[
  {
    "input_text": "Thyroid hormone receptors form distinct nuclear protein- dependent and independent complexes with a thyroid hormone response element .",
    "target_text": "<protein> Thyroid hormone receptors </protein> form distinct nuclear protein- dependent and independent complexes with a <DNA> thyroid hormone response element </DNA> ."
  },
  {
    "input_text": "We have examined the binding of nuclear proteins and recombinant thyroid hormone receptors ( TRs ) to the palindromic thyroid hormone responsive element AGGTCATGACCT ( TREp ) using a gel electrophoretic mobility shift assay .",
    "target_text": "We have examined the binding of <protein> nuclear proteins </protein> and <protein> recombinant thyroid hormone receptors </protein> ( <protein> TRs </protein> ) to the <DNA> palindromic thyroid hormone responsive element </DNA> AGGTCATGACCT ( <DNA> TREp </DNA> ) using a gel electrophoretic mobility shift assay ."
  },
  {
    "input_text": "Four specific protein-DNA complexes were detected after incubation of nuclear extracts ( NE ) from T3-responsive pituitary ( GH3 ) cells with a TREp -containing DNA fragment .",
    "target_text": "Four specific <protein> protein-DNA complexes </protein> were detected after incubation of nuclear extracts ( NE ) from <cell_line> T3-responsive pituitary ( GH3 ) cells </cell_line> with a <DNA> <DNA> TREp </DNA> -containing DNA fragment </DNA> ."
  },
  {
    "input_text": "This was compared with the TREp binding of reticulocyte lysate-synthesized TRs .",
    "target_text": "This was compared with the <DNA> TREp </DNA> binding of <protein> reticulocyte lysate-synthesized <protein> TRs </protein> </protein> ."
  },
  {
    "input_text": "TR alpha 1 and TR beta 2 each formed a single major TR : TREp complex which comigrated with the least retarded complex formed by GH3 NE , while TR beta 1 formed multiple complexes suggesting that it can bind to TREp as an oligomer .",
    "target_text": "<protein> TR alpha 1 </protein> and <protein> TR beta 2 </protein> each formed a single major <protein> <protein> TR </protein> : <DNA> TREp </DNA> complex </protein> which comigrated with the least retarded complex formed by GH3 NE , while <protein> TR beta 1 </protein> formed multiple complexes suggesting that it can bind to <DNA> TREp </DNA> as an <protein> oligomer </protein> ."
  },
  {
    "input_text": "Interestingly , coincubation of 35S- TR alpha 1 , GH3 NE , and unlabeled TREp resulted in not only the 35S-TR : TREp complex , but in two additional more greatly retarded complexes containing 35S- TR alpha 1 and comigrating with those formed by GH3 extract alone .",
    "target_text": "Interestingly , coincubation of <protein> 35S- <protein> TR alpha 1 </protein> </protein> , GH3 NE , and unlabeled <DNA> TREp </DNA> resulted in not only the <protein> 35S-TR : <DNA> TREp </DNA> complex </protein> , but in two additional more greatly retarded complexes containing <protein> 35S- <protein> TR alpha 1 </protein> </protein> and comigrating with those formed by GH3 extract alone ."
  },
  {
    "input_text": "Incubation of each of the TRs with NE from COS-7 cells , which do not possess sufficient endogenous TRs to mediate T3-responses , resulted in formation of a new , more greatly shifted complex .",
    "target_text": "Incubation of each of the <protein> TRs </protein> with NE from <cell_line> COS-7 cells </cell_line> , which do not possess sufficient endogenous <protein> TRs </protein> to mediate T3-responses , resulted in formation of a new , more <protein> greatly shifted complex </protein> ."
  },
  {
    "input_text": "A similar , heat labile activity which altered mobility of the TR : TRE complex was also present in NE from T3-unresponsive JEG-3 cells .",
    "target_text": "A similar , heat labile activity which altered mobility of the <protein> TR : TRE complex </protein> was also present in NE from <cell_line> T3-unresponsive JEG-3 cells </cell_line> ."
  },
  {
    "input_text": "At high concentration of NE , all of the TR bound to TREp was more greatly retarded than in the absence of NE .",
    "target_text": "At high concentration of NE , all of the <protein> TR </protein> bound to <DNA> TREp </DNA> was more greatly retarded than in the absence of NE ."
  },
  {
    "input_text": "Truncation of TR alpha 1 at amino acid 210 prevented additional complex formation in the presence of NE without affecting DNA binding , suggesting that the carboxyl-terminus of the TRs is essential for interaction with nuclear proteins .",
    "target_text": "Truncation of <protein> TR alpha 1 </protein> at <protein> amino acid 210 </protein> prevented additional complex formation in the presence of NE without affecting DNA binding , suggesting that the <protein> carboxyl-terminus </protein> of the <protein> TRs </protein> is essential for interaction with <protein> nuclear proteins </protein> ."
  },
  {
    "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )",
    "target_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"
  },
  {
    "input_text": "Cell-specific differences in activation of NF-kappa B regulatory elements of human immunodeficiency virus and beta interferon promoters by tumor necrosis factor .",
    "target_text": "Cell-specific differences in activation of <DNA> <protein> NF-kappa B </protein> regulatory elements </DNA> of human immunodeficiency virus and beta interferon promoters by <protein> tumor necrosis factor </protein> ."
  },
  {
    "input_text": "Three aspects of the involvement of tumor necrosis factor in human immunodeficiency virus ( HIV ) pathogenesis were examined .",
    "target_text": "Three aspects of the involvement of <protein> tumor necrosis factor </protein> in human immunodeficiency virus ( HIV ) pathogenesis were examined ."
  },
  {
    "input_text": "Tumor necrosis factor alpha ( TNF-alpha ) mRNA production was analyzed by polymerase chain reaction amplification in monocytic U937 cells and in a chronically HIV infected U937 cell line ( U9-IIIB ) .",
    "target_text": "<RNA> <protein> Tumor necrosis factor alpha </protein> ( <protein> TNF-alpha </protein> ) mRNA </RNA> production was analyzed by polymerase chain reaction amplification in <cell_line> monocytic U937 cells </cell_line> and in a <cell_line> chronically HIV infected U937 cell line </cell_line> ( <cell_line> U9-IIIB </cell_line> ) ."
  },
  {
    "input_text": "TNF-alpha RNA was undetectable in U937 cells , whereas a low constitutive level was detected in U9-IIIB cells .",
    "target_text": "<RNA> <protein> TNF-alpha </protein> RNA </RNA> was undetectable in <cell_line> U937 cells </cell_line> , whereas a low constitutive level was detected in <cell_line> U9-IIIB cells </cell_line> ."
  },
  {
    "input_text": "Paramyxovirus infection induced a 5- to 10-fold increase in the steady-state level of TNF-alpha RNA in U9-IIIB cells compared with U937 cells , suggesting that HIV-infected monocytic cells produced higher levels of TNF-alpha than did normal cells after a secondary virus infection .",
    "target_text": "Paramyxovirus infection induced a 5- to 10-fold increase in the steady-state level of <RNA> <protein> TNF-alpha </protein> RNA </RNA> in <cell_line> U9-IIIB cells </cell_line> compared with <cell_line> U937 cells </cell_line> , suggesting that <cell_line> HIV-infected monocytic cells </cell_line> produced higher levels of <protein> TNF-alpha </protein> than did normal cells after a secondary virus infection ."
  },
  {
    "input_text": "The effects of TNF-alpha on gene expression were examined by transient expression assays using reporter chloramphenicol acetyltransferase plasmids linked to regulatory elements from the HIV long terminal repeat ( LTR ) and the beta interferon promoter .",
    "target_text": "The effects of <protein> TNF-alpha </protein> on gene expression were examined by transient expression assays using <DNA> reporter chloramphenicol acetyltransferase plasmids </DNA> linked to <DNA> regulatory elements </DNA> from the <DNA> HIV long terminal repeat </DNA> ( <DNA> LTR </DNA> ) and the <DNA> beta interferon promoter </DNA> ."
  },
  {
    "input_text": "In U937 and Jurkat T lymphoid cells , the inducibility of the different hybrid promoters by TNF-alpha or phorbol ester varied in a cell type- and promoter context-specific manner ; the levels of gene activity of NF-kappa B -containing plasmids correlated directly with induction of NF-kappa B DNA-binding activity .",
    "target_text": "In U937 and Jurkat T lymphoid cells , the inducibility of the different <DNA> hybrid promoters </DNA> by <protein> TNF-alpha </protein> or phorbol ester varied in a cell type- and promoter context-specific manner ; the levels of gene activity of <DNA> <protein> NF-kappa B </protein> -containing plasmids </DNA> correlated directly with induction of <protein> NF-kappa B </protein> DNA-binding activity ."
  },
  {
    "input_text": "Although the intact beta interferon promoter was only weakly stimulated by phorbol ester or TNF-alpha , multimers of the PRDII NF-kappa B -binding domain were inducible by both agents .",
    "target_text": "Although the intact <DNA> beta interferon promoter </DNA> was only weakly stimulated by phorbol ester or <protein> TNF-alpha </protein> , multimers of the <DNA> PRDII <protein> NF-kappa B </protein> -binding domain </DNA> were inducible by both agents ."
  },
  {
    "input_text": "TNF-alpha was able to increase expression of the HIV LTR in T cells , but in monocytic cells , TNF-alpha did not induce the HIV LTR above a constitutive level of activity .",
    "target_text": "<protein> TNF-alpha </protein> was able to increase expression of the <DNA> HIV LTR </DNA> in <cell_type> T cells </cell_type> , but in <cell_type> monocytic cells </cell_type> , <protein> TNF-alpha </protein> did not induce the <DNA> HIV LTR </DNA> above a constitutive level of activity ."
  },
  {
    "input_text": "This level of NF-kappa B -independent activity appears to be sufficient for virus multiplication , since TNF-alpha treatment had no effect on the kinetics of de novo HIV type 1 ( HIV-1 ) infection and viral RNA production in U937 cells .",
    "target_text": "This level of <protein> NF-kappa B </protein> -independent activity appears to be sufficient for virus multiplication , since <protein> TNF-alpha </protein> treatment had no effect on the kinetics of de novo HIV type 1 ( HIV-1 ) infection and <RNA> viral RNA </RNA> production in <cell_line> U937 cells </cell_line> ."
  },
  {
    "input_text": "However , in Jurkat cells , TNF-alpha dramatically enhanced the spread of HIV-1 through the cell population and increased viral RNA synthesis , indicating that in T cells HIV-1 multiplication was stimulated by TNF-alpha treatment .",
    "target_text": "However , in <cell_line> Jurkat cells </cell_line> , <protein> TNF-alpha </protein> dramatically enhanced the spread of HIV-1 through the cell population and increased <RNA> viral RNA </RNA> synthesis , indicating that in <cell_type> T cells </cell_type> HIV-1 multiplication was stimulated by <protein> TNF-alpha </protein> treatment ."
  },
  {
    "input_text": "Functional analysis of cis-linked regulatory sequences in the HLA DRA promoter by transcription in vitro .",
    "target_text": "Functional analysis of <DNA> cis-linked regulatory sequences </DNA> in the <DNA> HLA DRA promoter </DNA> by transcription in vitro ."
  },
  {
    "input_text": "Two consensus sequences , called X and Y boxes , capable of binding nuclear proteins and regulating expression in B cells have been defined within the immediate upstream region of major histocompatibility complex ( MHC ) class II promoters .",
    "target_text": "Two consensus sequences , called X and Y boxes , capable of binding <protein> nuclear proteins </protein> and regulating expression in <cell_type> B cells </cell_type> have been defined within the immediate upstream region of <DNA> major histocompatibility complex ( MHC ) class II promoters </DNA> ."
  },
  {
    "input_text": "Unlike other class II promoters , the HLA-DR alpha ( DRA ) promoter also contains one element identical to the \" octamer \" motif of immunoglobulin variable region promoters that is responsible for B cell-specific transcription .",
    "target_text": "Unlike other <DNA> class II promoters </DNA> , the <DNA> HLA-DR alpha ( DRA ) promoter </DNA> also contains one element identical to the <DNA> \" octamer \" motif </DNA> of <DNA> immunoglobulin variable region promoters </DNA> that is responsible for B cell-specific transcription ."
  },
  {
    "input_text": "This \" octamer \" in the context of DRA appears capable of binding both the ubiquitous ( OTF-1 ) and lymphoid-specific ( OTF-2 ) \" octamer \" binding proteins , but at least one other distinct \" octamer \" complex was found .",
    "target_text": "This \" <DNA> octamer </DNA> \" in the context of <protein> DRA </protein> appears capable of binding both the <protein> ubiquitous </protein> ( <protein> OTF-1 </protein> ) and <protein> lymphoid-specific ( <protein> OTF-2 </protein> ) \" octamer \" binding proteins </protein> , but at least one other distinct <protein> \" octamer \" complex </protein> was found ."
  },
  {
    "input_text": "In order to characterize the function of cis-acting elements , we have developed an in vitro system in which a DRA promoter construct is transcribed more efficiently in extracts from B cells than in extracts from class II-negative HeLa cells .",
    "target_text": "In order to characterize the function of <DNA> cis-acting elements </DNA> , we have developed an in vitro system in which a <DNA> DRA promoter construct </DNA> is transcribed more efficiently in extracts from <cell_type> B cells </cell_type> than in extracts from <cell_line> class II-negative HeLa cells </cell_line> ."
  },
  {
    "input_text": "5' deletion constructs which lacked the Y box , but retained the \" octamer \" motif and TATA box were completely inactive , and internal deletion of the Y box reduced transcription by 95 % .",
    "target_text": "5' deletion constructs which lacked the <DNA> Y box </DNA> , but retained the <DNA> \" octamer \" motif </DNA> and <DNA> TATA box </DNA> were completely inactive , and internal deletion of the <DNA> Y box </DNA> reduced transcription by 95 % ."
  },
  {
    "input_text": "Using supercoiled , but not linear templates , we observed differences in transcription efficiencies from templates lacking or disrupting the X consensus element that reflect effects of random replacement of X box sequences in transient expression assays .",
    "target_text": "Using supercoiled , but not linear templates , we observed differences in transcription efficiencies from templates lacking or disrupting the <DNA> X consensus element </DNA> that reflect effects of random replacement of <DNA> X box sequences </DNA> in transient expression assays ."
  },
  {
    "input_text": "Demonstration of the complete dependence on the Y box in this system suggests that , despite its demonstrated importance in the DRA promoter , the DRA \" octamer \" does not utilize OTF-2 in a manner analogous to immunoglobulin promoters in B cells .",
    "target_text": "Demonstration of the complete dependence on the <DNA> Y box </DNA> in this system suggests that , despite its demonstrated importance in the <DNA> DRA promoter </DNA> , the <DNA> DRA \" octamer \" </DNA> does not utilize <protein> OTF-2 </protein> in a manner analogous to <DNA> immunoglobulin promoters </DNA> in <cell_type> B cells </cell_type> ."
  },
  {
    "input_text": "Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression .",
    "target_text": "Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression ."
  },
  {
    "input_text": "Lipopolysaccharide ( LPS ) potently stimulates human immunodeficiency virus type 1-long terminal repeat ( HIV-1-LTR ) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line .",
    "target_text": "Lipopolysaccharide ( LPS ) potently stimulates <DNA> <DNA> human immunodeficiency virus type 1-long terminal repeat </DNA> ( <DNA> HIV-1-LTR </DNA> ) CAT constructs </DNA> transfected into <cell_line> monocyte/macrophage-like cell lines </cell_line> but not a <cell_line> T cell line </cell_line> ."
  },
  {
    "input_text": "This effect appears to be mediated through the induction of nuclear factor kappa B ( NF-kappa B ) .",
    "target_text": "This effect appears to be mediated through the induction of <protein> nuclear factor kappa B </protein> ( <protein> NF-kappa B </protein> ) ."
  },
  {
    "input_text": "Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells .",
    "target_text": "Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from <protein> NF-kappa B </protein> in <cell_line> U937 </cell_line> and <cell_line> THP-1 cells </cell_line> ."
  },
  {
    "input_text": "LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line , U1 , which produces very low levels of HIV-1 at baseline .",
    "target_text": "LPS is also shown to dramatically increase HIV-1 production from a <cell_line> chronically infected monocyte/macrophage-like cloned cell line </cell_line> , <cell_line> U1 </cell_line> , which produces very low levels of HIV-1 at baseline ."
  },
  {
    "input_text": "The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor ( GM-CSF ) before treatment with LPS .",
    "target_text": "The stimulation of viral production from this cell line occurs only if these cells are treated with <protein> granulocyte/macrophage colony-stimulating factor </protein> ( <protein> GM-CSF </protein> ) before treatment with LPS ."
  },
  {
    "input_text": "This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B .",
    "target_text": "This stimulation of HIV-1 production is correlated with an increase in the level of <RNA> HIV-1 RNA </RNA> and and activation of <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "LPS is not able to induce HIV-1 production in a cloned T cell line .",
    "target_text": "LPS is not able to induce HIV-1 production in a cloned <cell_line> T cell line </cell_line> ."
  },
  {
    "input_text": "The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection .",
    "target_text": "The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection ."
  },
  {
    "input_text": "Steroid dose sparing : pharmacodynamic responses to single versus divided doses of methylprednisolone in man .",
    "target_text": "Steroid dose sparing : pharmacodynamic responses to single versus divided doses of methylprednisolone in man ."
  },
  {
    "input_text": "Inhibitory drug interactions affecting the metabolism of methylprednisolone ( MP ) may produce either steroid sparing or adverse effects partly by increasing the exposure time to the steroid .",
    "target_text": "Inhibitory drug interactions affecting the metabolism of methylprednisolone ( MP ) may produce either steroid sparing or adverse effects partly by increasing the exposure time to the steroid ."
  },
  {
    "input_text": "This phenomenon can be mimicked by administering MP in divided doses .",
    "target_text": "This phenomenon can be mimicked by administering MP in divided doses ."
  },
  {
    "input_text": "Two types of responses were compared after a single MP dose ( 40 mg bolus ) and a divided regimen ( 20 mg bolus and a 5 mg bolus 8 hours later ) in six healthy male volunteers .",
    "target_text": "Two types of responses were compared after a single MP dose ( 40 mg bolus ) and a divided regimen ( 20 mg bolus and a 5 mg bolus 8 hours later ) in six healthy male volunteers ."
  },
  {
    "input_text": "The suppression of basophils measured as whole blood histamine and plasma cortisol concentrations was assessed during 32 hours .",
    "target_text": "The suppression of <cell_type> basophils </cell_type> measured as whole blood histamine and plasma cortisol concentrations was assessed during 32 hours ."
  },
  {
    "input_text": "The 37.5 % reduction in dose produced a 23 % overall decreased blood histamine response .",
    "target_text": "The 37.5 % reduction in dose produced a 23 % overall decreased blood histamine response ."
  },
  {
    "input_text": "A pharmacodynamic model for basophil cell distribution to and from an extravascular compartment describes the effects of MP after both regimens .",
    "target_text": "A pharmacodynamic model for basophil cell distribution to and from an extravascular compartment describes the effects of MP after both regimens ."
  },
  {
    "input_text": "A slower initial decline in blood histamine after the divided regimen may be related to incomplete suppression of basophil cell return to blood .",
    "target_text": "A slower initial decline in blood histamine after the divided regimen may be related to incomplete suppression of <cell_type> basophil cell </cell_type> return to blood ."
  },
  {
    "input_text": "The 50 % inhibitory concentrations of MP of about 5 ng/ml were similar for both regimens .",
    "target_text": "The 50 % inhibitory concentrations of MP of about 5 ng/ml were similar for both regimens ."
  },
  {
    "input_text": "The decline and return of cortisol concentrations were similar between MP treatments with suppression continuing for 24 hours .",
    "target_text": "The decline and return of cortisol concentrations were similar between MP treatments with suppression continuing for 24 hours ."
  },
  {
    "input_text": "The 50 % inhibitory concentrations of MP values for adrenal suppression were about 1 ng/ml .",
    "target_text": "The 50 % inhibitory concentrations of MP values for adrenal suppression were about 1 ng/ml ."
  },
  {
    "input_text": "Pharmacodynamic modeling is useful in quantitating corticosteroid responses and generally predicted the \" dose-sparing \" effects that were achieved by prolonging MP plasma concentrations .",
    "target_text": "Pharmacodynamic modeling is useful in quantitating corticosteroid responses and generally predicted the \" dose-sparing \" effects that were achieved by prolonging MP plasma concentrations ."
  },
  {
    "input_text": "This study supports previous clinical observations that patients may require morning through evening exposure to MP to optimize efficacy while adrenal suppression is being minimized .",
    "target_text": "This study supports previous clinical observations that patients may require morning through evening exposure to MP to optimize efficacy while adrenal suppression is being minimized ."
  },
  {
    "input_text": "1,25(OH)2D2 production by T lymphocytes and alveolar macrophages recovered by lavage from normocalcemic patients with tuberculosis .",
    "target_text": "1,25(OH)2D2 production by <cell_type> T lymphocytes </cell_type> and <cell_type> alveolar macrophages </cell_type> recovered by lavage from normocalcemic patients with tuberculosis ."
  },
  {
    "input_text": "To compare extra-renal 1,25(OH)2D3 production in different types of granulomatous disease , and to identify the cell types responsible , we have evaluated the conversion of 25(OH)D3 in 1,25(OH)2D3 by uncultured cells recovered by bronchoalveolar lavage and blood mononuclear cells from normocalcemic patients with sarcoidosis and tuberculosis .",
    "target_text": "To compare extra-renal 1,25(OH)2D3 production in different types of granulomatous disease , and to identify the cell types responsible , we have evaluated the conversion of 25(OH)D3 in 1,25(OH)2D3 by <cell_type> uncultured cells </cell_type> recovered by bronchoalveolar lavage and <cell_type> blood mononuclear cells </cell_type> from normocalcemic patients with sarcoidosis and tuberculosis ."
  },
  {
    "input_text": "1,25(OH)2D3 was produced both by lavage cells ( 12/12 tuberculosis patients , 2/6 sarcoidosis patients ) and blood mononuclear cells ( 3/5 tuberculosis patients , 0/3 sarcoidosis patients ) from patients but not controls , but significantly greater amounts were produced by lavage cells from tuberculosis patients than those of sarcoidosis patients ( P less than 0.001 ) .",
    "target_text": "1,25(OH)2D3 was produced both by <cell_type> lavage cells </cell_type> ( 12/12 tuberculosis patients , 2/6 sarcoidosis patients ) and <cell_type> blood mononuclear cells </cell_type> ( 3/5 tuberculosis patients , 0/3 sarcoidosis patients ) from patients but not controls , but significantly greater amounts were produced by lavage cells from tuberculosis patients than those of sarcoidosis patients ( P less than 0.001 ) ."
  },
  {
    "input_text": "1,25(OH)2D3 production by lavage cells from tuberculosis patients correlated with the number of CD8+ T lymphocytes present but not other cell types .",
    "target_text": "1,25(OH)2D3 production by <cell_type> lavage cells </cell_type> from tuberculosis patients correlated with the number of CD8+ <cell_type> T lymphocytes </cell_type> present but not other cell types ."
  },
  {
    "input_text": "T lymphocytes appeared to be an important source of 1,25(OH)2D3 production , since purified T lymphocytes from all patients with tuberculosis produced 1,25(OH)2D3 , and 1,25(OH)2D3 production by these cells correlated closely with that produced by unseparated lavage cells .",
    "target_text": "<cell_type> T lymphocytes </cell_type> appeared to be an important source of 1,25(OH)2D3 production , since purified <cell_type> T lymphocytes </cell_type> from all patients with tuberculosis produced 1,25(OH)2D3 , and 1,25(OH)2D3 production by these cells correlated closely with that produced by unseparated <cell_type> lavage cells </cell_type> ."
  },
  {
    "input_text": "Because 1,25(OH)2D3 can improve the capacity of macrophages to kill mycobacteria , our results support the conclusion that macrophage-lymphocyte interactions , mediated at least in part by 1,25(OH)2D3 , may be an important component of a successful antituberculous immune response .",
    "target_text": "Because 1,25(OH)2D3 can improve the capacity of <cell_type> macrophages </cell_type> to kill mycobacteria , our results support the conclusion that macrophage-lymphocyte interactions , mediated at least in part by 1,25(OH)2D3 , may be an important component of a successful antituberculous immune response ."
  },
  {
    "input_text": "Megakaryocytic and erythrocytic lineages share specific transcription factors .",
    "target_text": "Megakaryocytic and erythrocytic lineages share specific <protein> transcription factors </protein> ."
  },
  {
    "input_text": "Erythroid-specific genes contain binding sites for NF-E1 ( also called GF-1 and Eryf-1 ; refs 1-3 respectively ) , the principal DNA-binding protein of the erythrocytic lineage .",
    "target_text": "<DNA> Erythroid-specific genes </DNA> contain binding sites for <protein> NF-E1 </protein> ( also called <protein> GF-1 </protein> and <protein> Eryf-1 </protein> ; refs 1-3 respectively ) , the principal <protein> DNA-binding protein </protein> of the <cell_type> erythrocytic lineage </cell_type> ."
  },
  {
    "input_text": "NF-E1 expression seems to be restricted to the erythrocytic lineage .",
    "target_text": "<protein> NF-E1 </protein> expression seems to be restricted to the <cell_type> erythrocytic lineage </cell_type> ."
  },
  {
    "input_text": "A closely related ( if not identical ) protein is found in both a human megakaryocytic cell line and purified human megakaryocytes ; it binds to promoter regions of two megakaryocytic-specific genes .",
    "target_text": "A closely related ( if not identical ) protein is found in both a <cell_line> human megakaryocytic cell line </cell_line> and <cell_line> purified human megakaryocytes </cell_line> ; it binds to <DNA> promoter regions </DNA> of two <DNA> megakaryocytic-specific genes </DNA> ."
  },
  {
    "input_text": "The binding sites and partial proteolysis profile of this protein are indistinguishable from those of the erythroid protein ; also , NF-E1 messenger RNA is the same size in both the megakaryocytic and erythroid cell lines .",
    "target_text": "The binding sites and partial proteolysis profile of this protein are indistinguishable from those of the <protein> erythroid protein </protein> ; also , <RNA> <protein> NF-E1 </protein> messenger RNA </RNA> is the same size in both the megakaryocytic and erythroid cell lines ."
  },
  {
    "input_text": "Furthermore , point mutations that abolish binding of NF-E1 result in a 70 % decrease in the transcriptional activity of a megakaryocytic-specific promoter .",
    "target_text": "Furthermore , point mutations that abolish binding of <protein> NF-E1 </protein> result in a 70 % decrease in the transcriptional activity of a <DNA> megakaryocytic-specific promoter </DNA> ."
  },
  {
    "input_text": "We also find that NF-E2 , another trans-acting factor of the erythrocytic lineage , is present in megakaryocytes .",
    "target_text": "We also find that <protein> NF-E2 </protein> , another <protein> trans-acting factor </protein> of the <cell_type> erythrocytic lineage </cell_type> , is present in <cell_line> megakaryocytes </cell_line> ."
  },
  {
    "input_text": "Transcriptional effects in both lineages might then be mediated in part by the same specific trans-acting factors .",
    "target_text": "Transcriptional effects in both lineages might then be mediated in part by the same specific <protein> trans-acting factors </protein> ."
  },
  {
    "input_text": "Our data strengthen the idea of a close association between the erythrocytic and the megakaryocytic lineages and could also explain the expression of markers specific to the erythrocytic and megakaryocytic lineages in most erythroblastic and megakaryoblastic permanent cell lines .",
    "target_text": "Our data strengthen the idea of a close association between the erythrocytic and the megakaryocytic lineages and could also explain the expression of markers specific to the erythrocytic and megakaryocytic lineages in most erythroblastic and megakaryoblastic permanent cell lines ."
  },
  {
    "input_text": "Transcriptional down-regulation of c-myc expression by protein synthesis -dependent and -independent pathways in a human T lymphoblastic tumor cell line .",
    "target_text": "Transcriptional down-regulation of <DNA> c-myc </DNA> expression by protein synthesis -dependent and -independent pathways in a <cell_line> human T lymphoblastic tumor cell line </cell_line> ."
  },
  {
    "input_text": "We show that in the human T lymphoblastic tumor cell line Molt4 c-myc mRNA and protein expression is down-regulated after exposure to dimethyl sulfoxide , to phorbol myristate acetate , or to the calcium ionophore A23187 , which raises the intracellular calcium concentration .",
    "target_text": "We show that in the <cell_line> human T lymphoblastic tumor cell line </cell_line> <RNA> Molt4 <DNA> c-myc </DNA> mRNA </RNA> and protein expression is down-regulated after exposure to dimethyl sulfoxide , to phorbol myristate acetate , or to the calcium ionophore A23187 , which raises the intracellular calcium concentration ."
  },
  {
    "input_text": "A block to RNA elongation is largely responsible for decreased c-myc transcription .",
    "target_text": "A block to RNA elongation is largely responsible for decreased <DNA> c-myc </DNA> transcription ."
  },
  {
    "input_text": "Although negative regulation by dimethyl sulfoxide takes place even when protein synthesis is inhibited by cycloheximide , the phorbol myristate acetate effect is blocked to some extent only by cycloheximide .",
    "target_text": "Although negative regulation by dimethyl sulfoxide takes place even when protein synthesis is inhibited by cycloheximide , the phorbol myristate acetate effect is blocked to some extent only by cycloheximide ."
  },
  {
    "input_text": "The calcium ionophore-induced c-myc suppression , however , strictly requires de novo protein synthesis .",
    "target_text": "The calcium ionophore-induced <DNA> c-myc </DNA> suppression , however , strictly requires de novo protein synthesis ."
  },
  {
    "input_text": "Therefore , two different negative regulatory pathways are involved in c-myc regulation : one which is independent and one which depends on de novo protein synthesis .",
    "target_text": "Therefore , two different negative regulatory pathways are involved in <DNA> c-myc </DNA> regulation : one which is independent and one which depends on de novo protein synthesis ."
  },
  {
    "input_text": "The latter one appears to be mediated by a rapidly calcium -dependent induced gene product .",
    "target_text": "The latter one appears to be mediated by a rapidly <protein> calcium -dependent induced gene product </protein> ."
  },
  {
    "input_text": "Oestrogen receptor ( ER ) analysis in B-cell chronic lymphocytic leukemia : correlation of biochemical and immunocytochemical methods .",
    "target_text": "<protein> Oestrogen receptor </protein> ( <protein> ER </protein> ) analysis in B-cell chronic lymphocytic leukemia : correlation of biochemical and immunocytochemical methods ."
  },
  {
    "input_text": "Oestrogen receptors ( ER ) are present in neoplastic lymphoid cells and have been considered a physiological marker of growth rate or differentiation .",
    "target_text": "<protein> Oestrogen receptors </protein> ( <protein> ER </protein> ) are present in <cell_type> neoplastic lymphoid cells </cell_type> and have been considered a physiological marker of growth rate or differentiation ."
  },
  {
    "input_text": "Tamoxifen , an oestrogen antagonist , has been given in some patients with CLL and Hodgkin 's disease , with dramatic response in single cases .",
    "target_text": "Tamoxifen , an oestrogen antagonist , has been given in some patients with CLL and Hodgkin 's disease , with dramatic response in single cases ."
  },
  {
    "input_text": "Until now , ER status has been assessed using a steroid binding assay ( SBA ) which has many inherent problems .",
    "target_text": "Until now , <protein> ER </protein> status has been assessed using a steroid binding assay ( SBA ) which has many inherent problems ."
  },
  {
    "input_text": "Recently , the development of monoclonal antibodies directed against ER has been applied to the study of breast carcinomas and results obtained show good correlation with the quantitative SBA .",
    "target_text": "Recently , the development of monoclonal antibodies directed against <protein> ER </protein> has been applied to the study of breast carcinomas and results obtained show good correlation with the quantitative SBA ."
  },
  {
    "input_text": "We studied 49 cases of B-cell chronic lymphocytic leukemia ( CLL ) using immunostaining of cytospin preparations .",
    "target_text": "We studied 49 cases of B-cell chronic lymphocytic leukemia ( CLL ) using immunostaining of cytospin preparations ."
  },
  {
    "input_text": "In 30 of these cases ER enzyme immunoassay ( ER -EIA ) was also performed .",
    "target_text": "In 30 of these cases <protein> ER </protein> enzyme immunoassay ( <protein> ER </protein> -EIA ) was also performed ."
  },
  {
    "input_text": "Cultured MCF-7 cells , derived from a pleural effusion of a breast cancer patient , known to contain high levels of ER were used as a positive control ( 40-48 % ER positive cells by immunocytochemistry ; 200 fmol/mg protein by EIA ) .",
    "target_text": "<cell_line> Cultured MCF-7 cells </cell_line> , derived from a pleural effusion of a breast cancer patient , known to contain high levels of <protein> ER </protein> were used as a positive control ( 40-48 % <cell_type> <protein> ER </protein> positive cells </cell_type> by immunocytochemistry ; 200 fmol/mg protein by EIA ) ."
  },
  {
    "input_text": "All of the CLL cases except two ( 96 % ) were negative for ER ( less than 1 % staining ; less than 4 fmol/mg protein ) .",
    "target_text": "All of the CLL cases except two ( 96 % ) were negative for <protein> ER </protein> ( less than 1 % staining ; less than 4 fmol/mg protein ) ."
  },
  {
    "input_text": "The two positive cases expressed granular ER staining over the nucleus ( 9.2 and 12.1 % positive cells ) and were positive by EIA and SBA .",
    "target_text": "The two positive cases expressed granular <protein> ER </protein> staining over the nucleus ( 9.2 and 12.1 % positive cells ) and were positive by EIA and SBA ."
  },
  {
    "input_text": "It is concluded that ( i ) patients with CLL rarely express ER and ( ii ) immunocytochemical staining of cytospin preparations is a valid technique for the measurement of ER .",
    "target_text": "It is concluded that ( i ) patients with CLL rarely express <protein> ER </protein> and ( ii ) immunocytochemical staining of cytospin preparations is a valid technique for the measurement of <protein> ER </protein> ."
  },
  {
    "input_text": "It is of interest that one of the positive cases was diagnosed as CLL with Richter 's transformation confirming earlier findings .",
    "target_text": "It is of interest that one of the positive cases was diagnosed as CLL with Richter 's transformation confirming earlier findings ."
  },
  {
    "input_text": "Type-II estrogen binding sites in a lymphoblastoid cell line and growth-inhibitory effect of estrogen , anti-estrogen and bioflavonoids .",
    "target_text": "<protein> Type-II estrogen binding sites </protein> in a <cell_line> lymphoblastoid cell line </cell_line> and growth-inhibitory effect of estrogen , anti-estrogen and bioflavonoids ."
  },
  {
    "input_text": "Type-II estrogen -binding sites ( type-II EBS ) have been demonstrated in the human lymphoblastoid cell line IM-9 using a whole-cell assay with ( 6,7-3H ) estradiol ( 3H-E2 ) as tracer .",
    "target_text": "<protein> Type-II estrogen -binding sites </protein> ( <protein> type-II EBS </protein> ) have been demonstrated in the <cell_line> human <cell_line> lymphoblastoid cell line </cell_line> </cell_line> <cell_line> IM-9 </cell_line> using a whole-cell assay with ( 6,7-3H ) estradiol ( 3H-E2 ) as tracer ."
  },
  {
    "input_text": "Competition analysis showed that the anti-estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)-E2 binding to type-II EBS .",
    "target_text": "Competition analysis showed that the anti-estrogen tamoxifen and the flavonoids quercetin and rutin competed for (3H)-E2 binding to <protein> type-II EBS </protein> ."
  },
  {
    "input_text": "Growth experiments demonstrated that diethylstilbestrol ( DES ) tamoxifen ( TAM ) , quercetin and rutin exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM .",
    "target_text": "Growth experiments demonstrated that diethylstilbestrol ( DES ) tamoxifen ( TAM ) , quercetin and rutin exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM ."
  },
  {
    "input_text": "The relative binding affinity of quercetin , rutin , DES and TAM for type-II EBS correlated well with their potency as cell growth inhibitors .",
    "target_text": "The relative binding affinity of quercetin , rutin , DES and TAM for <protein> type-II EBS </protein> correlated well with their potency as cell growth inhibitors ."
  },
  {
    "input_text": "Moreover , hesperidin , a flavonoid which does not bind to type-II EBS , was ineffective in inhibiting cell growth .",
    "target_text": "Moreover , hesperidin , a flavonoid which does not bind to <protein> type-II EBS </protein> , was ineffective in inhibiting cell growth ."
  },
  {
    "input_text": "Cell-cycle analysis showed that the growth-inhibitory effect of DES , TAM or quercetin was due to a blocking effect in the G0-G1 phases .",
    "target_text": "Cell-cycle analysis showed that the growth-inhibitory effect of DES , TAM or quercetin was due to a blocking effect in the G0-G1 phases ."
  },
  {
    "input_text": "Our results suggest that high estrogen and anti-estrogen concentrations and flavonoids may regulate IM-9 cell growth through a common mechanism involving a binding interaction with type-II EBS .",
    "target_text": "Our results suggest that high estrogen and anti-estrogen concentrations and flavonoids may regulate <cell_line> IM-9 </cell_line> cell growth through a common mechanism involving a binding interaction with <protein> type-II EBS </protein> ."
  },
  {
    "input_text": "[ Glucocorticoid receptors in peripheral blood lymphocytes of patients with bronchial asthma ]",
    "target_text": "[ <protein> Glucocorticoid receptors </protein> in <cell_type> peripheral blood lymphocytes </cell_type> of patients with bronchial asthma ]"
  },
  {
    "input_text": "Quantitation of glucocorticoid receptors ( GCR ) and the study of their affinity for glucocorticosteroids ( GCS ) were made in peripheral blood lymphocytes of bronchial asthma ( BA ) patients in consideration of GCR treatment and serum levels of endogenous cortisol .",
    "target_text": "Quantitation of <protein> glucocorticoid receptors </protein> ( <protein> GCR </protein> ) and the study of their affinity for glucocorticosteroids ( GCS ) were made in <cell_type> peripheral blood lymphocytes </cell_type> of bronchial asthma ( BA ) patients in consideration of <protein> GCR </protein> treatment and serum levels of endogenous cortisol ."
  },
  {
    "input_text": "It is stated that GCR of healthy controls and GCS -untreated patients outnumbered those of cortisol-dependent BA patients on hormone therapy .",
    "target_text": "It is stated that <protein> GCR </protein> of healthy controls and GCS -untreated patients outnumbered those of cortisol-dependent BA patients on hormone therapy ."
  },
  {
    "input_text": "Following discontinuation of glucocorticoid drugs GCR count in cortisol -dependent BA tends to rise .",
    "target_text": "Following discontinuation of glucocorticoid drugs <protein> GCR </protein> count in cortisol -dependent BA tends to rise ."
  },
  {
    "input_text": "Endogenous cortisol has no effect on GCR level estimated by 3H-triamcinolone acetonide .",
    "target_text": "Endogenous cortisol has no effect on <protein> GCR </protein> level estimated by 3H-triamcinolone acetonide ."
  },
  {
    "input_text": "Two glucocorticoid binding sites on the human glucocorticoid receptor .",
    "target_text": "Two <protein> glucocorticoid binding sites </protein> on the <protein> human glucocorticoid receptor </protein> ."
  },
  {
    "input_text": "Glucocorticoids are known to have a lytic effect in leukemic cells via interactions with the glucocorticoid receptor ( GR ) .",
    "target_text": "Glucocorticoids are known to have a lytic effect in <cell_type> leukemic cells </cell_type> via interactions with the <protein> glucocorticoid receptor </protein> ( <protein> GR </protein> ) ."
  },
  {
    "input_text": "Cortisol and various synthetic glucocorticoids bind to the GR with one-site kinetics .",
    "target_text": "Cortisol and various synthetic glucocorticoids bind to the <protein> GR </protein> with one-site kinetics ."
  },
  {
    "input_text": "Cortivazol ( CVZ ) is a unique , high potency synthetic glucocorticoid , which has a phenylpyrazol fused to the A-ring of the steroid nucleus and displays binding consistent with two or more sites in the cytosol from CEM C7 cells ( a human acute lymphoblastic T-cell line ) .",
    "target_text": "Cortivazol ( CVZ ) is a unique , high potency synthetic glucocorticoid , which has a phenylpyrazol fused to the A-ring of the steroid nucleus and displays binding consistent with two or more sites in the cytosol from <cell_line> CEM C7 cells </cell_line> ( a <cell_line> human acute lymphoblastic T-cell line </cell_line> ) ."
  },
  {
    "input_text": "It has previously been shown that the lower affinity class of sites are similar in affinity and site molarity to those recognized by dexamethasone .",
    "target_text": "It has previously been shown that the lower affinity class of sites are similar in affinity and site molarity to those recognized by dexamethasone ."
  },
  {
    "input_text": "The higher affinity sites bind CVZ with 20- to 50-fold greater affinity , consistent with CVZ 's enhanced biological effects .",
    "target_text": "The higher affinity sites bind CVZ with 20- to 50-fold greater affinity , consistent with CVZ 's enhanced biological effects ."
  },
  {
    "input_text": "In mutant leukemic cells resistant to the lytic effects of dexamethasone , CVZ both lyses the cells and recognizes a single class of sites similar to the high affinity site in CEM C7 cells .",
    "target_text": "In mutant <cell_type> leukemic cells </cell_type> resistant to the lytic effects of dexamethasone , CVZ both lyses the cells and recognizes a single class of sites similar to the high affinity site in <cell_line> CEM C7 cells </cell_line> ."
  },
  {
    "input_text": "We have carried out experiments to define the nature of the higher affinity CVZ binding site .",
    "target_text": "We have carried out experiments to define the nature of the <protein> higher affinity CVZ binding site </protein> ."
  },
  {
    "input_text": "We now show that : 1 ) CVZ has more than one binding site in a second , independent , B-cell line , IM-9 ; 2 ) the antiglucocorticoid RU 38486 is able to block both CVZ 's higher and lower affinity sites ; 3 ) all of CVZ 's binding sites are on a protein immunologically indistinguishable from the human GR ; and 4 ) freshly isolated clones of CVZ -resistant cells have lost all binding sites for CVZ .",
    "target_text": "We now show that : 1 ) CVZ has more than one binding site in a second , independent , <cell_line> B-cell line </cell_line> , <cell_line> IM-9 </cell_line> ; 2 ) the antiglucocorticoid RU 38486 is able to block both CVZ 's higher and lower affinity sites ; 3 ) all of <protein> CVZ 's binding sites </protein> are on a protein immunologically indistinguishable from the human <protein> GR </protein> ; and 4 ) freshly isolated clones of CVZ -resistant cells have lost all binding sites for CVZ ."
  },
  {
    "input_text": "These data indicate that CVZ is recognizing two glucocorticoid binding sites on the human GR or a protein very similar to it .",
    "target_text": "These data indicate that CVZ is recognizing two <protein> glucocorticoid binding sites </protein> on the human <protein> GR </protein> or a protein very similar to it ."
  },
  {
    "input_text": "Retroviral mediated transfer and expression of exogenous genes in primary lymphoid cells : assaying for a viral transactivator activity in normal and malignant cells .",
    "target_text": "Retroviral mediated transfer and expression of <DNA> exogenous genes </DNA> in <cell_type> primary lymphoid cells </cell_type> : assaying for a viral <protein> transactivator </protein> activity in normal and malignant cells ."
  },
  {
    "input_text": "In this report we describe the use of recombinant retroviruses to characterize the activity of an exogenous promoter in primary cells obtained from patients with lymphoproliferative disorders .",
    "target_text": "In this report we describe the use of recombinant retroviruses to characterize the activity of an <DNA> exogenous promoter </DNA> in primary cells obtained from patients with lymphoproliferative disorders ."
  },
  {
    "input_text": "The infection of a variety of cultured and primary lymphoid cells with a recombinant retrovirus containing a histone promoter-driven beta-galactosidase gene is shown to result in the expression of beta-galactosidase in 50 % to 100 % of the cells .",
    "target_text": "The infection of a variety of cultured and <cell_type> primary lymphoid cells </cell_type> with a recombinant retrovirus containing a <DNA> <protein> histone promoter-driven beta-galactosidase </protein> gene </DNA> is shown to result in the expression of <protein> beta-galactosidase </protein> in 50 % to 100 % of the cells ."
  },
  {
    "input_text": "A similar infection with a recombinant retrovirus containing the beta-galactosidase gene with an adenovirus E2 promoter , results in beta-galactosidase activity in a limited number of cultured and primary cells .",
    "target_text": "A similar infection with a recombinant retrovirus containing the <DNA> <protein> beta-galactosidase </protein> gene </DNA> with an <DNA> adenovirus E2 promoter </DNA> , results in <protein> beta-galactosidase </protein> activity in a limited number of <cell_line> cultured </cell_line> and <cell_type> primary cells </cell_type> ."
  },
  {
    "input_text": "Since the adenovirus E2 promoter has been well characterized and is known to be regulated by transactivators encoded by many viruses , the activity of this promoter in specific cell types is discussed in reference to both the biology of the cell and the possible presence of as yet undetected viral gene products .",
    "target_text": "Since the <DNA> adenovirus E2 promoter </DNA> has been well characterized and is known to be regulated by <protein> transactivators </protein> encoded by many viruses , the activity of this promoter in specific cell types is discussed in reference to both the biology of the cell and the possible presence of as yet undetected <protein> viral gene products </protein> ."
  },
  {
    "input_text": "[ The effect of 24,25-dihydroxyvitamin D3 ( dioxyvit ) on Ca metabolism and immune status during chronic kidney failure ]",
    "target_text": "[ The effect of 24,25-dihydroxyvitamin D3 ( dioxyvit ) on Ca metabolism and immune status during chronic kidney failure ]"
  },
  {
    "input_text": "Active metabolite of vitamin D3 , 24R,25 (OH)2D3 ( dioxyvit ) was used at a daily dose of 100 micrograms in treatment of children affected with tubulointerstitial disease of kidney and with chronic glomerulonephritis under conditions of kidney insufficiency .",
    "target_text": "Active metabolite of vitamin D3 , 24R,25 (OH)2D3 ( dioxyvit ) was used at a daily dose of 100 micrograms in treatment of children affected with tubulointerstitial disease of kidney and with chronic glomerulonephritis under conditions of kidney insufficiency ."
  },
  {
    "input_text": "The drug exhibited distinct normalizing effect on patterns of calcium metabolism : increase of total and ionized Ca2+ and of 25-OHD , decrease in concentration of parath hormone and osteocalcine in blood serum as well as on immunological parameters : restoration of decreased content of T- and 0- lymphocytes .",
    "target_text": "The drug exhibited distinct normalizing effect on patterns of calcium metabolism : increase of total and ionized Ca2+ and of 25-OHD , decrease in concentration of parath hormone and osteocalcine in blood serum as well as on immunological parameters : restoration of decreased content of T- and 0- lymphocytes ."
  },
  {
    "input_text": "Concentration of receptors of hormonal form of 1,25(OH)2D3 was found to be minimal in lymphocytes under conditions of chronic kidney insufficiency , while their expression , after the dioxyvit action , was detected only in patients with glomerulonephritis .",
    "target_text": "Concentration of receptors of hormonal form of 1,25(OH)2D3 was found to be minimal in <cell_type> lymphocytes </cell_type> under conditions of chronic kidney insufficiency , while their expression , after the dioxyvit action , was detected only in patients with glomerulonephritis ."
  },
  {
    "input_text": "Specific calcitropic effect of dioxyvit with simultaneous correction of vitamin D deficiency were apparently responsible for high efficacy of the drug in treatment of calcium metabolism and immunity impairments in children with renal deteriorations at the step of chronic kidney insufficiency .",
    "target_text": "Specific calcitropic effect of dioxyvit with simultaneous correction of vitamin D deficiency were apparently responsible for high efficacy of the drug in treatment of calcium metabolism and immunity impairments in children with renal deteriorations at the step of chronic kidney insufficiency ."
  },
  {
    "input_text": "[ The role of glucocorticoid receptors and HLA antigens in the pathogenesis of Cushing 's syndrome ]",
    "target_text": "[ The role of <protein> glucocorticoid receptors </protein> and <protein> HLA antigens </protein> in the pathogenesis of <protein> Cushing 's syndrome </protein> ]"
  },
  {
    "input_text": "Lymphocytic levels of glucocorticoid receptors were evaluated in 114 patients suffering from Icenko- Cushing 's syndrome .",
    "target_text": "Lymphocytic levels of <protein> glucocorticoid receptors </protein> were evaluated in 114 patients suffering from Icenko- <protein> Cushing 's syndrome </protein> ."
  },
  {
    "input_text": "Incidence of HLA antigens was determined in 94 of them .",
    "target_text": "Incidence of <protein> HLA antigens </protein> was determined in 94 of them ."
  },
  {
    "input_text": "A significant rise of A10 and B27 antigen incidence compared to that in normal subjects allows these antigens to be considered genetic markers of Icenko- Cushing 's syndrome .",
    "target_text": "A significant rise of <protein> A10 </protein> and <protein> B27 antigen </protein> incidence compared to that in normal subjects allows these antigens to be considered genetic markers of Icenko- <protein> Cushing 's syndrome </protein> ."
  },
  {
    "input_text": "The levels of glucocorticoid receptors in lymphocytes of the patients are lower than in normal subjects both in the active stage of the disease and following bilateral total adrenalectomy .",
    "target_text": "The levels of <protein> glucocorticoid receptors </protein> in <cell_type> lymphocytes </cell_type> of the patients are lower than in normal subjects both in the active stage of the disease and following bilateral total adrenalectomy ."
  },
  {
    "input_text": "The patients carrying B27 antigen had lymphocytic receptor concentrations under the levels of such in patients free of the antigen carriage .",
    "target_text": "The patients carrying <protein> B27 antigen </protein> had lymphocytic receptor concentrations under the levels of such in patients free of the antigen carriage ."
  },
  {
    "input_text": "Antigen B27 seems to be a cause of lower levels of glucocorticoid receptors in blood lymphocytes .",
    "target_text": "<protein> Antigen B27 </protein> seems to be a cause of lower levels of <protein> glucocorticoid receptors </protein> in <cell_type> blood <cell_type> lymphocytes </cell_type> </cell_type> ."
  },
  {
    "input_text": "Effects of 1 alpha , 25-dihydroxyvitamin D3 on the human chronic myelogenous leukemia cell line RWLeu-4 .",
    "target_text": "Effects of 1 alpha , 25-dihydroxyvitamin D3 on the <cell_line> human chronic myelogenous leukemia cell line </cell_line> <cell_line> RWLeu-4 </cell_line> ."
  },
  {
    "input_text": "The effects of 1 alpha , 25-dihydroxyvitamin D3 ( VD3 ) on proliferation , differentiation , and macromolecular synthesis in the new Philadelphia chromosome-positive chronic myelogenous leukemia cell line , RWLeu-4 , were investigated .",
    "target_text": "The effects of 1 alpha , 25-dihydroxyvitamin D3 ( VD3 ) on proliferation , differentiation , and macromolecular synthesis in the new <cell_line> Philadelphia chromosome-positive chronic myelogenous leukemia cell line </cell_line> , <cell_line> RWLeu-4 </cell_line> , were investigated ."
  },
  {
    "input_text": "Binding of [3H]VD3 was saturable , with approximately 2000-3000 sites/cell , and half-maximal binding occurring at 0.21-0.33 nM .",
    "target_text": "Binding of [3H]VD3 was saturable , with approximately 2000-3000 sites/cell , and half-maximal binding occurring at 0.21-0.33 nM ."
  },
  {
    "input_text": "Treatment of RWLeu-4 cells with VD3 induced 24R-hydroxylase activity , a marker of vitamin D3 responsiveness in many tissues .",
    "target_text": "Treatment of <cell_line> RWLeu-4 cells </cell_line> with VD3 induced <protein> 24R-hydroxylase </protein> activity , a marker of vitamin D3 responsiveness in many tissues ."
  },
  {
    "input_text": "Exposure of RWLeu-4 cells to VD3 also inhibited proliferation and DNA synthesis with a 50 % effective dose of 3.5-10 nM within 72 h ; in addition , protein and RNA synthesis were inhibited by VD3 treatment .",
    "target_text": "Exposure of <cell_line> RWLeu-4 cells </cell_line> to VD3 also inhibited proliferation and DNA synthesis with a 50 % effective dose of 3.5-10 nM within 72 h ; in addition , protein and RNA synthesis were inhibited by VD3 treatment ."
  },
  {
    "input_text": "Exposure of RWLeu-4 cells to 5 nM VD3 for 72 h caused 50 % of the cells to differentiate into macrophage/monocyte type cells as judged by nitroblue tetrazolium staining and adherence to plastic .",
    "target_text": "Exposure of <cell_line> RWLeu-4 cells </cell_line> to 5 nM VD3 for 72 h caused 50 % of the cells to differentiate into <cell_type> macrophage/monocyte type cells </cell_type> as judged by nitroblue tetrazolium staining and adherence to plastic ."
  },
  {
    "input_text": "Progressive expression of cell surface maturation-specific antigens of the monocyte/macrophage lineage was induced by treatment of RWLeu-4 cells with VD3 for 24 to 72 h at doses that inhibited cellular proliferation .",
    "target_text": "Progressive expression of <protein> cell surface maturation-specific antigens </protein> of the <cell_type> monocyte/macrophage lineage </cell_type> was induced by treatment of <cell_line> RWLeu-4 cells </cell_line> with VD3 for 24 to 72 h at doses that inhibited cellular proliferation ."
  },
  {
    "input_text": "c-myc RNA , which is constitutively expressed in RWLeu-4 cells , increased after 0.5 h of treatment with 50 nM VD3 and then rapidly decreased to barely detectable levels after 4 h of treatment .",
    "target_text": "<RNA> c-myc RNA </RNA> , which is constitutively expressed in <cell_line> RWLeu-4 cells </cell_line> , increased after 0.5 h of treatment with 50 nM VD3 and then rapidly decreased to barely detectable levels after 4 h of treatment ."
  },
  {
    "input_text": "Finally , the in vitro tyrosine kinase activity associated with the p210bcr-abl oncogene product was decreased approximately 50 % by VD3 treatment .",
    "target_text": "Finally , the in vitro tyrosine kinase activity associated with the <protein> <DNA> p210bcr-abl oncogene </DNA> product </protein> was decreased approximately 50 % by VD3 treatment ."
  },
  {
    "input_text": "Because of the presence of a functional receptor-effector system for VD3 and multiple biological responses to the hormone , these cells provide a unique model system with which to probe the specific effects of VD3 on cell growth and differentiation in chronic myelogenous leukemia .",
    "target_text": "Because of the presence of a functional receptor-effector system for VD3 and multiple biological responses to the hormone , these cells provide a unique model system with which to probe the specific effects of VD3 on cell growth and differentiation in chronic myelogenous leukemia ."
  },
  {
    "input_text": "A new member of the leucine zipper class of proteins that binds to the HLA DR alpha promoter .",
    "target_text": "A new member of the <protein> <protein> leucine zipper </protein> class </protein> of proteins that binds to the <DNA> HLA DR alpha promoter </DNA> ."
  },
  {
    "input_text": "Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex ( MHC ) class II genes .",
    "target_text": "Several mutants derived from <cell_line> transformed human B cell lines </cell_line> are defective in expressing <DNA> major histocompatibility complex ( MHC ) class II genes </DNA> ."
  },
  {
    "input_text": "The failure to express a class II gene in at least one such mutant line has been mapped to the MHC class II X box , a conserved transcriptional element in the promoter region .",
    "target_text": "The failure to express a <DNA> class II gene </DNA> in at least one such <cell_line> mutant line </cell_line> has been mapped to the <DNA> MHC class II X box </DNA> , a <DNA> conserved transcriptional element </DNA> in the <DNA> promoter region </DNA> ."
  },
  {
    "input_text": "A complementary DNA encoding a DNA-binding protein ( human X box binding protein , hXBP-1 ) whose target is the human DR alpha X box and the 3' flanking region has now been cloned .",
    "target_text": "A <DNA> complementary DNA </DNA> encoding a <protein> DNA-binding protein </protein> ( <protein> human X box binding protein </protein> , <protein> hXBP-1 </protein> ) whose target is the <DNA> human DR alpha X box </DNA> and the <DNA> 3' flanking region </DNA> has now been cloned ."
  },
  {
    "input_text": "This complementary DNA encoded a protein with structural similarities to the c-jun proto-oncogene product , and its target sequence was closely related to the palindromic target sequence of c-jun .",
    "target_text": "This <DNA> complementary DNA </DNA> encoded a protein with structural similarities to the <protein> c-jun proto-oncogene product </protein> , and its target sequence was closely related to the <DNA> palindromic target sequence </DNA> of <DNA> c-jun </DNA> ."
  },
  {
    "input_text": "Mutation of the hXBP-1 DNA target sequence decreased DR alpha promoter activity in vivo .",
    "target_text": "Mutation of the <DNA> <protein> hXBP-1 </protein> DNA target sequence </DNA> decreased <DNA> DR alpha promoter </DNA> activity in vivo ."
  },
  {
    "input_text": "These studies suggest that the hXBP-1 protein acts as a transcription factor in B cells .",
    "target_text": "These studies suggest that the <protein> <protein> hXBP-1 </protein> protein </protein> acts as a <protein> transcription factor </protein> in <cell_type> B cells </cell_type> ."
  },
  {
    "input_text": "Pseudohypoaldosteronism in eight families : different forms of inheritance are evidence for various genetic defects .",
    "target_text": "Pseudohypoaldosteronism in eight families : different forms of inheritance are evidence for various genetic defects ."
  },
  {
    "input_text": "Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone .",
    "target_text": "Pseudohypoaldosteronism is a rare hereditary disorder presenting in early infancy with renal salt loss leading to hyponatremia and hyperkalemia despite high levels of plasma aldosterone ."
  },
  {
    "input_text": "The patients are insensitive to mineralocorticoids ; however , sodium supplementation is able to correct electrolyte abnormalities .",
    "target_text": "The patients are insensitive to mineralocorticoids ; however , sodium supplementation is able to correct electrolyte abnormalities ."
  },
  {
    "input_text": "Absent or greatly diminished type I aldosterone receptors in peripheral mononuclear leucocytes have been recently demonstrated and explain the lack of response to mineralocorticoids .",
    "target_text": "Absent or greatly diminished type <protein> I aldosterone receptors </protein> in <cell_type> peripheral mononuclear leucocytes </cell_type> have been recently demonstrated and explain the lack of response to mineralocorticoids ."
  },
  {
    "input_text": "We have studied the mode of inheritance in eight families with a total of nine patients .",
    "target_text": "We have studied the mode of inheritance in eight families with a total of nine patients ."
  },
  {
    "input_text": "There was evidence for an autosomal recessive form of inheritance in four families , while the other four families appeared to have an autosomal dominant mode of transmission .",
    "target_text": "There was evidence for an autosomal recessive form of inheritance in four families , while the other four families appeared to have an autosomal dominant mode of transmission ."
  },
  {
    "input_text": "In three families the autosomal recessive form was characterized by normal receptor as well as hormone data in both parents , while in one family receptor levels in both parents were greatly reduced , but hormone levels were normal .",
    "target_text": "In three families the autosomal recessive form was characterized by <protein> normal receptor </protein> as well as hormone data in both parents , while in one family receptor levels in both parents were greatly reduced , but hormone levels were normal ."
  },
  {
    "input_text": "In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in peripheral mononuclear leucocytes and elevated serum hormone levels .",
    "target_text": "In the four families with an autosomal dominant mode of transmission there was always one parent with reduced receptor binding in <cell_type> peripheral mononuclear leucocytes </cell_type> and elevated serum hormone levels ."
  },
  {
    "input_text": "These parents were entirely asymptomatic .",
    "target_text": "These parents were entirely asymptomatic ."
  },
  {
    "input_text": "In an extended family we were able to study an aunt and her newborn daughter , who were both also biochemically affected but clinically asymptomatic .",
    "target_text": "In an extended family we were able to study an aunt and her newborn daughter , who were both also biochemically affected but clinically asymptomatic ."
  },
  {
    "input_text": "It , therefore , appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism .",
    "target_text": "It , therefore , appears that this dual pattern of genetic transmission may indicate differing genetic defects which cause the same clinical picture of pseudohypoaldosteronism ."
  },
  {
    "input_text": "Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients .",
    "target_text": "Perceived social support and tumor <protein> estrogen/progesterone receptor </protein> status as predictors of <protein> <cell_type> natural killer cell </cell_type> activity </protein> in breast cancer patients ."
  },
  {
    "input_text": "This report is concerned with the prediction of natural killer ( NK ) cell activity in 61 Stage I and II breast cancer patients , between the ages of 25 and 70 , who were accrued to this project .",
    "target_text": "This report is concerned with the prediction of natural <cell_type> killer ( NK ) cell </cell_type> activity in 61 Stage I and II breast cancer patients , between the ages of 25 and 70 , who were accrued to this project ."
  },
  {
    "input_text": "All baseline interview and testing data were obtained either just before patients were discharged from the hospital , or at their first outpatient visit , within two weeks of discharge .",
    "target_text": "All baseline interview and testing data were obtained either just before patients were discharged from the hospital , or at their first outpatient visit , within two weeks of discharge ."
  },
  {
    "input_text": "A major interest of this project is the predictive value of perceived social support , as a potential \" stress \" buffer , related to NK activity .",
    "target_text": "A major interest of this project is the predictive value of perceived social support , as a potential \" stress \" buffer , related to NK activity ."
  },
  {
    "input_text": "In the main model reported here , we found that a significant amount of NK activity variance could be explained by five variables .",
    "target_text": "In the main model reported here , we found that a significant amount of NK activity variance could be explained by five variables ."
  },
  {
    "input_text": "Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other , perceived social support from the patient 's physician , estrogen receptor -negative tumor status , having an excisional biopsy as surgical treatment , and actively seeking social support as a major coping strategy ( R2 = 0.33 , F ( 5 , 55 ) = 5.5 , p less than 0.0004 ) .",
    "target_text": "Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other , perceived social support from the patient 's physician , <protein> estrogen receptor </protein> -negative tumor status , having an <protein> excisional biopsy </protein> as <protein> surgical treatment </protein> , and actively seeking <protein> social support </protein> as a major coping strategy ( R2 = 0.33 , F ( 5 , 55 ) = 5.5 , p less than 0.0004 ) ."
  },
  {
    "input_text": "Findings are discussed in terms of host interaction with tumor endocrine status , and the role that social support might play in modulating such activity .",
    "target_text": "Findings are discussed in terms of host interaction with <protein> tumor endocrine status </protein> , and the role that <protein> social support </protein> might play in modulating such activity ."
  },
  {
    "input_text": "[ Estrogen receptor content of peripheral blood lymphocytes in patients with systemic lupus erythematosus ]",
    "target_text": "[ <protein> Estrogen receptor </protein> content of <cell_type> peripheral blood lymphocytes </cell_type> in patients with systemic lupus erythematosus ]"
  },
  {
    "input_text": "ER content in lymphocytes of peripheral blood from 27 SLE patients and 20 healthy controls were determined by dextran-coated charcoal assay .",
    "target_text": "ER content in <cell_type> lymphocytes </cell_type> of peripheral blood from 27 SLE patients and 20 healthy controls were determined by dextran-coated charcoal assay ."
  },
  {
    "input_text": "ER content in lymphocytes of each sample was expressed by both fmol/mg of lymphocyte cytosolic protein and fmol/micrograms of lymphocyte DNA .",
    "target_text": "<protein> ER </protein> content in <cell_type> lymphocytes </cell_type> of each sample was expressed by both fmol/mg of <protein> lymphocyte cytosolic protein </protein> and fmol/micrograms of <DNA> lymphocyte DNA </DNA> ."
  },
  {
    "input_text": "The results showed that there was no significant difference between the ER content of lymphocytes from the controls and that from patients with SLE .",
    "target_text": "The results showed that there was no significant difference between the <protein> ER </protein> content of <cell_type> lymphocytes </cell_type> from the controls and that from patients with SLE ."
  },
  {
    "input_text": "But the logarithmic mean of ER content in lymphocytes , expressed by fmol/mg of cytosolic protein , in 14 patients with active SLE ( 0.9356 +/- 0.31 ) was significantly higher than that in 13 patients with inactive SLE ( 0.2979 +/- 0.23 , P less than 0.001 ) and in the controls ( 0.6204 +/- 0.52 , P less than 0.001 ) .",
    "target_text": "But the logarithmic mean of <protein> ER </protein> content in <cell_type> lymphocytes </cell_type> , expressed by fmol/mg of <protein> cytosolic protein </protein> , in 14 patients with active SLE ( 0.9356 +/- 0.31 ) was significantly higher than that in 13 patients with inactive SLE ( 0.2979 +/- 0.23 , P less than 0.001 ) and in the controls ( 0.6204 +/- 0.52 , P less than 0.001 ) ."
  },
  {
    "input_text": "The normal upper limit of ER content in lymphocytes , expressed by fmol/micrograms of DNA , was 0.136 .",
    "target_text": "The normal upper limit of <protein> ER </protein> content in <cell_type> lymphocytes </cell_type> , expressed by fmol/micrograms of DNA , was 0.136 ."
  },
  {
    "input_text": "The elevated rate of ER content in lymphocytes in 14 active SLE ( 92.9 % ) was also higher than that in quieiescent patients ( 23.1 % , P less than 0.001 ) and in the controls ( 10 % , P less than 0.001 ) .",
    "target_text": "The elevated rate of <protein> ER </protein> content in <cell_type> lymphocytes </cell_type> in 14 active SLE ( 92.9 % ) was also higher than that in quieiescent patients ( 23.1 % , P less than 0.001 ) and in the controls ( 10 % , P less than 0.001 ) ."
  },
  {
    "input_text": "Moreover , the elevated level of ER content was found to be related to the positive antidsDNA antibody and hypocomplementemia .",
    "target_text": "Moreover , the elevated level of <protein> ER </protein> content was found to be related to the positive <protein> antidsDNA antibody </protein> and hypocomplementemia ."
  },
  {
    "input_text": "An in vitro globin gene switching model based on differentiated embryonic stem cells .",
    "target_text": "An in vitro <DNA> globin gene </DNA> switching model based on <cell_type> differentiated embryonic stem cells </cell_type> ."
  },
  {
    "input_text": "We used mouse embryonic stem ( ES ) cells to study globin gene expression and switching in vitro .",
    "target_text": "We used <cell_type> mouse embryonic stem ( ES ) cells </cell_type> to study <DNA> globin gene </DNA> expression and switching in vitro ."
  },
  {
    "input_text": "We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation , a switch occurs to the fetal/adult genes .",
    "target_text": "We show that <cell_type> ES-derived embryoid bodies </cell_type> express the full complement of <DNA> mouse embryonic globin genes </DNA> in the correct temporal order and that on further differentiation , a switch occurs to the <DNA> fetal/adult genes </DNA> ."
  },
  {
    "input_text": "In addition , the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies .",
    "target_text": "In addition , the <protein> erythroid-specific transcription factor </protein> <protein> NF-E1 </protein> was shown to be expressed coordinately with that of <protein> globin </protein> in <cell_type> embryoid bodies </cell_type> ."
  },
  {
    "input_text": "We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development .",
    "target_text": "We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development ."
  },
  {
    "input_text": "When the human epsilon- or beta- globin genes driven by the dominant control region ( DCR ) are introduced into this system , the human epsilon- globin gene , in contrast to the beta- globin gene , is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene .",
    "target_text": "When the human epsilon- or beta- globin genes driven by the <DNA> dominant control region </DNA> ( <DNA> DCR </DNA> ) are introduced into this system , the <DNA> human epsilon- <DNA> globin gene </DNA> </DNA> , in contrast to the <DNA> beta- <DNA> globin gene </DNA> </DNA> , is not deregulated by the presence of the <DNA> DCR </DNA> and is expressed strictly as an <DNA> embryonic gene </DNA> ."
  },
  {
    "input_text": "We conclude from this that the epsilon- globin gene is not regulated by competition with other genes in the human beta-globin locus .",
    "target_text": "We conclude from this that the <DNA> epsilon- <DNA> globin gene </DNA> </DNA> is not regulated by competition with other genes in the <DNA> human beta-globin locus </DNA> ."
  },
  {
    "input_text": "Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs .",
    "target_text": "Cloning of a <DNA> mitogen-inducible gene </DNA> encoding a <protein> kappa B DNA-binding protein </protein> with homology to the <DNA> rel oncogene </DNA> and to <DNA> cell-cycle motifs </DNA> ."
  },
  {
    "input_text": "We have cloned and characterized a mitogen-inducible gene isolated from human T cells that predicts a protein of 968 amino acids .",
    "target_text": "We have cloned and characterized a <DNA> mitogen-inducible gene </DNA> isolated from <cell_type> human T cells </cell_type> that predicts a protein of <protein> 968 amino acids </protein> ."
  },
  {
    "input_text": "The amino-terminal domain has regions homologous to the oncogene rel and to the developmentally important gene dorsal of Drosophila .",
    "target_text": "The <protein> amino-terminal domain </protein> has regions homologous to the <DNA> oncogene rel </DNA> and to the developmentally important gene <DNA> dorsal </DNA> of Drosophila ."
  },
  {
    "input_text": "The carboxy-terminal domain contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans , as well as in the putative human oncogene bcl-3 and in the ankyrin protein .",
    "target_text": "The <protein> carboxy-terminal domain </protein> contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans , as well as in the <DNA> putative human oncogene bcl-3 </DNA> and in the <protein> ankyrin protein </protein> ."
  },
  {
    "input_text": "A truncated form of the product of this gene translated in vitro is a DNA-binding protein which interacts specifically with the kappa B binding site found in many inducible genes , including the enhancer in human immunodeficiency virus .",
    "target_text": "A truncated form of the product of this gene translated in vitro is a <protein> DNA-binding protein </protein> which interacts specifically with the <DNA> kappa B binding site </DNA> found in many <DNA> inducible genes </DNA> , including the enhancer in human immunodeficiency virus ."
  },
  {
    "input_text": "This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation .",
    "target_text": "This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation ."
  },
  {
    "input_text": "Extrarenal receptor-effector-mechanisms for aldosterone : the sequence of effects on the cellular electrolyte transport in human lymphocytes and their implications for disorders of the water and electrolyte balances .",
    "target_text": "Extrarenal receptor-effector-mechanisms for aldosterone : the sequence of effects on the cellular electrolyte transport in <cell_type> human <cell_type> lymphocytes </cell_type> </cell_type> and their implications for disorders of the water and electrolyte balances ."
  },
  {
    "input_text": "High affinity aldosterone binding sites have not only been described in the classic target tissues such as the renal tubules , but also in non-classic target tissues such as the hippocampus , mammary gland , endothelial cells and , recently , human mononuclear leukocytes .",
    "target_text": "High affinity aldosterone binding sites have not only been described in the classic target tissues such as the renal tubules , but also in non-classic target tissues such as the hippocampus , mammary gland , <cell_type> endothelial cells </cell_type> and , recently , <cell_type> human mononuclear leukocytes </cell_type> ."
  },
  {
    "input_text": "An in vitro effect of aldosterone on intracellular sodium , potassium and calcium concentrations and cell volume was shown in human mononuclear leukocytes .",
    "target_text": "An in vitro effect of aldosterone on intracellular sodium , potassium and calcium concentrations and cell volume was shown in <cell_type> human mononuclear leukocytes </cell_type> ."
  },
  {
    "input_text": "In the absence of aldosterone , the intracellular Na+ , K+ and Ca2+ concentrations and the cell volume decreased significantly , but remained constant when aldosterone ( 1.4 nmol/l ) was added to the incubation medium .",
    "target_text": "In the absence of aldosterone , the intracellular Na+ , K+ and Ca2+ concentrations and the cell volume decreased significantly , but remained constant when aldosterone ( 1.4 nmol/l ) was added to the incubation medium ."
  },
  {
    "input_text": "These effects of aldosterone were blocked by the aldosterone antagonist canrenone ( 140 nmol/l ) .",
    "target_text": "These effects of aldosterone were blocked by the aldosterone antagonist canrenone ( 140 nmol/l ) ."
  },
  {
    "input_text": "The sodium/proton exchanger of the cell membrane could be identified as the primary target of the aldosterone action , possibly non-genomically mediated through membrane receptors .",
    "target_text": "The <protein> sodium/proton exchanger </protein> of the cell membrane could be identified as the primary target of the aldosterone action , possibly non-genomically mediated through <protein> membrane receptors </protein> ."
  },
  {
    "input_text": "The clinical significance of this model was underlined by the demonstration of absent or a decreased number of mineralocorticoid receptors and the lack of electrolyte response to aldosterone in human mononuclear leukocytes of patients with pseudohypoaldosteronism and aldosteronism .",
    "target_text": "The clinical significance of this model was underlined by the demonstration of absent or a decreased number of <protein> mineralocorticoid receptors </protein> and the lack of electrolyte response to aldosterone in <cell_type> human mononuclear leukocytes </cell_type> of patients with pseudohypoaldosteronism and aldosteronism ."
  },
  {
    "input_text": "Additionally , an abnormal effector mechanism could be demonstrated in human mononuclear leukocytes from essential hypertensives .",
    "target_text": "Additionally , an abnormal effector mechanism could be demonstrated in <cell_type> human mononuclear leukocytes </cell_type> from essential hypertensives ."
  },
  {
    "input_text": "These studies are the first to demonstrate the significance of extrarenal , nonepithelial mineralocorticoid receptors and the related effector mechanism in different disorders of the water and electrolyte balance in man .",
    "target_text": "These studies are the first to demonstrate the significance of <protein> extrarenal , nonepithelial <protein> mineralocorticoid receptors </protein> </protein> and the related effector mechanism in different disorders of the water and electrolyte balance in man ."
  },
  {
    "input_text": "Immunohistochemical study of steroid hormones and an estrogen binding assay in malignant soft tissue tumors .",
    "target_text": "Immunohistochemical study of steroid hormones and an estrogen binding assay in <cell_type> malignant soft tissue tumors </cell_type> ."
  },
  {
    "input_text": "Immunohistochemically , the immunoreaction against 5 steroid hormone anti-sera ( estradiol , estriol , cortisol , progesterone and testosterone ) was examined in 39 cases with the malignant soft tissue tumors ( fibrosarcoma : 8 , malignant fibrous histiocytoma : 6 , rhabdomyosarcoma : 10 , leiomyosarcoma : 10 , liposarcoma : 5 ) .",
    "target_text": "Immunohistochemically , the immunoreaction against 5 steroid hormone anti-sera ( estradiol , estriol , cortisol , progesterone and testosterone ) was examined in 39 cases with the <cell_type> malignant soft tissue tumors </cell_type> ( fibrosarcoma : 8 , malignant fibrous histiocytoma : 6 , rhabdomyosarcoma : 10 , leiomyosarcoma : 10 , liposarcoma : 5 ) ."
  },
  {
    "input_text": "Seventeen cases revealed distinct immunostaining against at least 1 of the 5 steroid hormones .",
    "target_text": "Seventeen cases revealed distinct immunostaining against at least 1 of the 5 steroid hormones ."
  },
  {
    "input_text": "Immunostained tumor cells were more frequently distributed in the area where tumor cell infiltration was more invasive .",
    "target_text": "<cell_type> Immunostained tumor cells </cell_type> were more frequently distributed in the area where tumor cell infiltration was more invasive ."
  },
  {
    "input_text": "The majority of the positive cases occurred in female cases .",
    "target_text": "The majority of the positive cases occurred in female cases ."
  },
  {
    "input_text": "Furthermore , the existence of estrogen receptor ( estrogen binding activity ) was examined histochemically in 39 cases and it was detected in 8 .",
    "target_text": "Furthermore , the existence of <protein> estrogen receptor </protein> ( estrogen binding activity ) was examined histochemically in 39 cases and it was detected in 8 ."
  },
  {
    "input_text": "We concluded that steroid hormones might be closely related to tumor cell infiltration of some malignant soft tissue tumors .",
    "target_text": "We concluded that steroid hormones might be closely related to tumor cell infiltration of some <cell_type> malignant soft tissue tumors </cell_type> ."
  },
  {
    "input_text": "Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1 .",
    "target_text": "Involvement of <protein> cyclic AMP-dependent protein kinases </protein> in the signal transduction pathway for <protein> interleukin-1 </protein> ."
  },
  {
    "input_text": "Expression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 ( IL-1 ) -responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat .",
    "target_text": "Expression of a highly specific protein inhibitor for <protein> cyclic AMP-dependent protein kinases </protein> in <cell_line> <protein> interleukin-1 </protein> ( IL-1 ) -responsive cells </cell_line> blocked <DNA> IL-1-induced gene </DNA> transcription that was driven by the <DNA> kappa immunoglobulin enhancer </DNA> or the <DNA> human immunodeficiency virus long terminal repeat </DNA> ."
  },
  {
    "input_text": "This inhibitor did not affect protein kinase C -mediated gene transcription , suggesting that cyclic AMP-dependent protein kinases are involved in the signal transduction pathway for IL-1 in a number of responsive cell types .",
    "target_text": "This inhibitor did not affect <protein> protein kinase C </protein> -mediated gene transcription , suggesting that <protein> cyclic AMP-dependent protein kinases </protein> are involved in the signal transduction pathway for <protein> IL-1 </protein> in a number of <cell_type> responsive cell types </cell_type> ."
  },
  {
    "input_text": "The Epstein-Barr virus ( EBV ) ORI1yt enhancer is not B-cell specific and does not respond synergistically to the EBV transcription factors R and Z .",
    "target_text": "The <DNA> Epstein-Barr virus ( EBV ) ORI1yt enhancer </DNA> is not B-cell specific and does not respond synergistically to the EBV transcription factors R and Z ."
  },
  {
    "input_text": "The Epstein-Barr virus DR promoter is located upstream of the PstI repeats , and in addition to the TATA box , it contains an upstream region ( positions -69 to -220 ) responsive to EB1 (Z) ( the BZLF1-encoded transcription factor ) and an enhancer with two functionally distinct domains , A and B .",
    "target_text": "The <DNA> Epstein-Barr virus DR promoter </DNA> is located upstream of the <DNA> PstI repeats </DNA> , and in addition to the <DNA> TATA box </DNA> , it contains an <DNA> upstream region </DNA> ( positions -69 to -220 ) responsive to <protein> EB1 (Z) </protein> ( the <protein> BZLF1-encoded transcription factor </protein> ) and an <DNA> enhancer </DNA> with two functionally distinct domains , <DNA> A </DNA> and <DNA> B </DNA> ."
  },
  {
    "input_text": "Domain B has been described as a B-cell-specific EB1 -responsive element ( P.M.Lieberman , J.M.Hardwick , and S.D.Hayward , J.Virol.63 : 3040-3050 , 1989 ) activated synergistically by EB1 and R , an EBV early product encoded by the open reading frame BRLF1 ( M.A. Cox , J.Leahy , and J.M.Hardwick , J.Virol.64 : 313-321 , 1990 ) .",
    "target_text": "<DNA> Domain B </DNA> has been described as a <DNA> B-cell-specific <protein> EB1 </protein> -responsive element </DNA> ( P.M.Lieberman , J.M.Hardwick , and S.D.Hayward , J.Virol.63 : 3040-3050 , 1989 ) activated synergistically by <protein> EB1 </protein> and <protein> R </protein> , an <protein> EBV early product </protein> encoded by the <DNA> open reading frame <DNA> BRLF1 </DNA> </DNA> ( M.A. Cox , J.Leahy , and J.M.Hardwick , J.Virol.64 : 313-321 , 1990 ) ."
  },
  {
    "input_text": "We show here that domain B is an R-responsive element in HeLa cells and is therefore not an EB1 -responsive B-cell-specific element .",
    "target_text": "We show here that <DNA> domain B </DNA> is an <DNA> R-responsive element </DNA> in <cell_line> HeLa cells </cell_line> and is therefore not an <DNA> <protein> EB1 </protein> -responsive B-cell-specific element </DNA> ."
  },
  {
    "input_text": "However , there is an EB1 -binding site ( ZRE-B ) located within the R-responsive enhancer region .",
    "target_text": "However , there is an <DNA> <protein> EB1 </protein> -binding site </DNA> ( <DNA> ZRE-B </DNA> ) located within the <DNA> R-responsive enhancer region </DNA> ."
  },
  {
    "input_text": "ZRE-B can be deleted without affecting the R-dependent enhancer activity .",
    "target_text": "<DNA> ZRE-B </DNA> can be deleted without affecting the R-dependent enhancer activity ."
  },
  {
    "input_text": "Moreover , there is no cooperation or synergy between R and EB1 when activating the B domain ( ZRE-B plus the R-responsive element ) positioned as an enhancer .",
    "target_text": "Moreover , there is no cooperation or synergy between <protein> R </protein> and <protein> EB1 </protein> when activating the <DNA> B domain </DNA> ( <DNA> ZRE-B </DNA> plus the <DNA> R-responsive element </DNA> ) positioned as an <DNA> enhancer </DNA> ."
  },
  {
    "input_text": "ZRE-B is therefore not part of the R- inducible enhancer .",
    "target_text": "<DNA> ZRE-B </DNA> is therefore not part of the <DNA> R- inducible enhancer </DNA> ."
  },
  {
    "input_text": "We have tested several subregions of the DR enhancer B domain , either alone or in combination , for their capacity to transmit the R-activating signal to the rabbit beta-globin promoter .",
    "target_text": "We have tested several subregions of the <DNA> DR enhancer </DNA> <DNA> B domain </DNA> , either alone or in combination , for their capacity to transmit the R-activating signal to the <DNA> rabbit beta-globin promoter </DNA> ."
  },
  {
    "input_text": "We found that the R-responsive element is composed of four protoenhancers that span the whole B domain .",
    "target_text": "We found that the <DNA> R-responsive element </DNA> is composed of four <DNA> protoenhancers </DNA> that span the whole <DNA> B domain </DNA> ."
  },
  {
    "input_text": "These protoenhancers alone are weakly or not responsive to R .",
    "target_text": "These <DNA> protoenhancers </DNA> alone are weakly or not responsive to <protein> R </protein> ."
  },
  {
    "input_text": "One of the protoenhancers contains the overlapping palindromes 5'-TTGTCCcgtGGACAAaTGTCC-3' .",
    "target_text": "One of the <DNA> protoenhancers </DNA> contains the <DNA> overlapping palindromes </DNA> 5'-TTGTCCcgtGGACAAaTGTCC-3' ."
  },
  {
    "input_text": "However , one palindrome , either alone or duplicated , or the overlapping palindromes did not respond to R .",
    "target_text": "However , one <DNA> palindrome </DNA> , either alone or duplicated , or the <DNA> overlapping palindromes </DNA> did not respond to R ."
  },
  {
    "input_text": "Nuclear 3,5,3'-triiodothyronine receptors ( T3R ) of circulating human lymphocytes in hyper- and hypo thyroidism and nonthyroidal diseases .",
    "target_text": "Nuclear <protein> 3,5,3'-triiodothyronine receptors </protein> ( <protein> T3R </protein> ) of <cell_type> circulating human <cell_type> lymphocytes </cell_type> </cell_type> in hyper- and hypo thyroidism and nonthyroidal diseases ."
  },
  {
    "input_text": "The clinical implications of nuclear T3R alterations of circulating lymphocytes in hyperthyroidism , hypothyroidism and nonthyroidal diseases were investigated .",
    "target_text": "The clinical implications of nuclear <protein> T3R </protein> alterations of <cell_type> circulating <cell_type> lymphocytes </cell_type> </cell_type> in hyperthyroidism , hypothyroidism and nonthyroidal diseases were investigated ."
  },
  {
    "input_text": "Nuclear T3R in lymphocytes was determined by radio-ligand binding analysis .",
    "target_text": "Nuclear <protein> T3R </protein> in <cell_type> lymphocytes </cell_type> was determined by radio-ligand binding analysis ."
  },
  {
    "input_text": "The results showed that in hyper- and hypo thyroid patients the nuclear affinity ( Ka ) for T3 was similar to that of normal subjects .",
    "target_text": "The results showed that in hyper- and hypo thyroid patients the nuclear affinity ( Ka ) for T3 was similar to that of normal subjects ."
  },
  {
    "input_text": "In hyperthyroidism nuclear T3 maximal binding capacity ( MBC ) was unaltered , whereas in hypothyroidism the MBC was significantly increased .",
    "target_text": "In hyperthyroidism nuclear T3 maximal binding capacity ( MBC ) was unaltered , whereas in hypothyroidism the MBC was significantly increased ."
  },
  {
    "input_text": "In the patients with diabetes mellitus , chronic renal failure and hepatic cirrhosis , the nuclear T3R MBC of lymphocytes was about 1.5-1.6 times of the normal controls .",
    "target_text": "In the patients with diabetes mellitus , chronic renal failure and hepatic cirrhosis , the <protein> nuclear <protein> T3R </protein> </protein> MBC of <cell_type> lymphocytes </cell_type> was about 1.5-1.6 times of the normal controls ."
  },
  {
    "input_text": "It was concluded that there existed hormonal regulation of nuclear T3R , and up-regulation was seen in hypothyroidism and low T3 syndrome .",
    "target_text": "It was concluded that there existed hormonal regulation of <protein> nuclear <protein> T3R </protein> </protein> , and up-regulation was seen in hypothyroidism and low T3 syndrome ."
  },
  {
    "input_text": "Lymphocyte cell lines from vitamin D-dependent rickets type II show functional defects in the 1 alpha,25-dihydroxyvitamin D3 receptor .",
    "target_text": "<cell_line> Lymphocyte cell lines </cell_line> from vitamin D-dependent rickets type II show functional defects in the <protein> 1 alpha,25-dihydroxyvitamin D3 receptor </protein> ."
  },
  {
    "input_text": "Lymphocyte cell lines were established from five patients with vitamin D-dependent rickets , type II ( VDDR-II ) .",
    "target_text": "<cell_line> Lymphocyte cell lines </cell_line> were established from five patients with vitamin D-dependent rickets , type II ( VDDR-II ) ."
  },
  {
    "input_text": "These lines were established by infection with human T-lymphotrophic virus type I ( HTLV-I ) .",
    "target_text": "These lines were established by infection with human T-lymphotrophic virus type I ( HTLV-I ) ."
  },
  {
    "input_text": "Binding of [3H]1 alpha,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) to its receptor in these cell lines was compared to binding studies using a T-lymphocyte cell line ( S-LB1 ) from a normal individual .",
    "target_text": "Binding of [3H]1 alpha,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) to its receptor in these cell lines was compared to binding studies using a <cell_line> T-lymphocyte cell line </cell_line> ( <cell_line> S-LB1 </cell_line> ) from a normal individual ."
  },
  {
    "input_text": "The 1,25(OH)2D3 receptor of S-LB1 was comparable to the well-characterized chick intestinal 1,25(OH)2D3 receptor in terms of its ligand binding affinity and capacity , its mobility on 5-20 % sucrose gradients , and its adsorption to and elution properties from DNA-cellulose .",
    "target_text": "The 1,25(OH)2D3 receptor of <cell_line> S-LB1 </cell_line> was comparable to the well-characterized <protein> chick intestinal 1,25(OH)2D3 receptor </protein> in terms of its ligand binding affinity and capacity , its mobility on 5-20 % sucrose gradients , and its adsorption to and elution properties from DNA-cellulose ."
  },
  {
    "input_text": "Three cell lines established from patients with VDDR-II ( Rh- VDR , Sh- VDR , and Ab- VDR ) showed no specific binding of 1,25(OH)2D3 to a receptor and treatment of the cultured cells with 1,25(OH)2D3 did not stimulate production of 24,25-dihydroxy-vitamin D3 ( 24,25(OH)2D3 ) , a response which is diagnostic of the presence of a functional 1,25(OH)2D3 receptor .",
    "target_text": "Three <cell_line> cell lines </cell_line> established from patients with VDDR-II ( Rh- <protein> VDR </protein> , Sh- <protein> VDR </protein> , and Ab- <protein> VDR </protein> ) showed no specific binding of 1,25(OH)2D3 to a <protein> receptor </protein> and treatment of the <cell_line> cultured cells </cell_line> with 1,25(OH)2D3 did not stimulate production of 24,25-dihydroxy-vitamin D3 ( 24,25(OH)2D3 ) , a response which is diagnostic of the presence of a <protein> functional 1,25(OH)2D3 receptor </protein> ."
  },
  {
    "input_text": "In a fourth cell line , A1-VDR , the receptor for 1,25(OH)2D3 had a low binding capacity and 25(OH)D3-24-hydroxylase activity was not detectable .",
    "target_text": "In a fourth <cell_line> cell line </cell_line> , <cell_line> A1-VDR </cell_line> , the receptor for 1,25(OH)2D3 had a low binding capacity and <protein> 25(OH)D3-24-hydroxylase </protein> activity was not detectable ."
  },
  {
    "input_text": "Induction of 24,25-(OH)2D3 synthesis by 1,25(OH)2D3 was observed in the fifth cell line , designated Ro-VDR , although the sensitivity to hormone treatment was lower than in the control cell line from a normal donor .",
    "target_text": "Induction of 24,25-(OH)2D3 synthesis by 1,25(OH)2D3 was observed in the fifth <cell_line> cell line </cell_line> , designated <cell_line> Ro-VDR </cell_line> , although the sensitivity to hormone treatment was lower than in the <cell_line> control cell line </cell_line> from a normal donor ."
  },
  {
    "input_text": "The capacity of the receptor for 1,25(OH)2D3 was low in Ro-VDR .",
    "target_text": "The capacity of the <protein> receptor </protein> for 1,25(OH)2D3 was low in <cell_line> Ro-VDR </cell_line> ."
  },
  {
    "input_text": "In all cell lines where 1,25(OH)2D3 binding to a receptor was detectable , the receptor had the typical sedimentation coefficient of 3.7 S on sucrose density gradient analysis .",
    "target_text": "In all <cell_line> cell lines </cell_line> where 1,25(OH)2D3 binding to a <protein> receptor </protein> was detectable , the <protein> receptor </protein> had the typical sedimentation coefficient of 3.7 S on sucrose density gradient analysis ."
  },
  {
    "input_text": "Binding and elution properties to DNA-cellulose , however , differed from normal in both Ro-VDR and A1-VDR cells where elution from DNA-cellulose occurred at a lower salt concentration than is typical of the 1,25(OH)2D3 receptor .",
    "target_text": "Binding and elution properties to DNA-cellulose , however , differed from normal in both <cell_line> Ro-VDR </cell_line> and <cell_line> <cell_line> A1-VDR </cell_line> cells </cell_line> where elution from DNA-cellulose occurred at a lower salt concentration than is typical of the <protein> 1,25(OH)2D3 <protein> receptor </protein> </protein> ."
  },
  {
    "input_text": "While Ro-VDR cells showed typical nuclear localization of the unoccupied 1,25(OH)2D3 receptor , neither the unoccupied nor the occupied receptor from A1-VDR cells was completely localized in the nucleus .",
    "target_text": "While <cell_line> <cell_line> Ro-VDR </cell_line> cells </cell_line> showed typical nuclear localization of the <protein> unoccupied 1,25(OH)2D3 <protein> receptor </protein> </protein> , neither the unoccupied nor the occupied <protein> receptor </protein> from <cell_line> <cell_line> A1-VDR </cell_line> cells </cell_line> was completely localized in the nucleus ."
  },
  {
    "input_text": "In a series of functional studies we found that modulation of the level of the mRNAs coding for both the c-myc oncogene and the growth factor known as granulocyte-monocyte colony stimulating activity by 1,25(OH)2D3 correlated with the 1,25(OH)2D3 receptor status of these cells .",
    "target_text": "In a series of functional studies we found that modulation of the level of the <RNA> mRNAs </RNA> coding for both the <DNA> c-myc oncogene </DNA> and the growth factor known as granulocyte-monocyte colony stimulating activity by 1,25(OH)2D3 correlated with the <protein> 1,25(OH)2D3 <protein> receptor </protein> </protein> status of these cells ."
  },
  {
    "input_text": "Use of these cell lines will facilitate further study of the molecular defect ( s ) in the receptor for 1,25(OH)2D3 in vitamin D-dependent rickets type II and will allow a correlation with impairment of cellular functions .",
    "target_text": "Use of these <cell_line> cell lines </cell_line> will facilitate further study of the molecular defect ( s ) in the <protein> receptor </protein> for 1,25(OH)2D3 in vitamin D-dependent rickets type II and will allow a correlation with impairment of cellular functions ."
  },
  {
    "input_text": "Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells .",
    "target_text": "Transcriptional and post-transcriptional regulation of <DNA> c-jun </DNA> expression during monocytic differentiation of <cell_line> human myeloid leukemic cells </cell_line> ."
  },
  {
    "input_text": "AP-1 , the polypeptide product of c-jun , recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate ( TPA ) .",
    "target_text": "<protein> AP-1 </protein> , the polypeptide product of <DNA> c-jun </DNA> , recognizes and binds to <DNA> specific DNA sequences </DNA> and stimulates transcription of <DNA> genes </DNA> responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate ( TPA ) ."
  },
  {
    "input_text": "We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation .",
    "target_text": "We studied the effects of TPA on the regulation of <DNA> c-jun </DNA> gene expression in <cell_line> HL-60 cells </cell_line> during monocytic differentiation ."
  },
  {
    "input_text": "Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells , increased significantly by 6 h , and reached near maximal levels by 24 h of exposure to 32 nM TPA .",
    "target_text": "Low levels of <RNA> <DNA> c-jun </DNA> transcripts </RNA> were detectable in <cell_line> untreated HL-60 leukemic cells </cell_line> , increased significantly by 6 h , and reached near maximal levels by 24 h of exposure to 32 nM TPA ."
  },
  {
    "input_text": "Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells .",
    "target_text": "Similar kinetics of <DNA> c-jun </DNA> induction by TPA were observed in <cell_line> human U-937 </cell_line> and <cell_line> THP-1 monocytic leukemia cells </cell_line> ."
  },
  {
    "input_text": "Similar findings were obtained with bryostatin 1 ( 10 nM ) , another activator of protein kinase C and inducer of monocytic differentiation .",
    "target_text": "Similar findings were obtained with bryostatin 1 ( 10 nM ) , another activator of <protein> protein kinase C </protein> and inducer of monocytic differentiation ."
  },
  {
    "input_text": "Furthermore , 1,25-dihydroxyvitamin D3 ( 0.5 microM ) , a structurally distinct agent which also induces HL-60 monocytic differentiation , increased c-jun expression .",
    "target_text": "Furthermore , 1,25-dihydroxyvitamin D3 ( 0.5 microM ) , a structurally distinct agent which also induces HL-60 monocytic differentiation , increased <DNA> c-jun </DNA> expression ."
  },
  {
    "input_text": "TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts .",
    "target_text": "TPA treatment of <cell_line> HL-60 cells </cell_line> in the presence of cycloheximide was associated with superinduction of <DNA> c-jun </DNA> transcripts ."
  },
  {
    "input_text": "Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells , and that exposure to TPA increases this rate 3.3-fold .",
    "target_text": "Run-on analysis demonstrated detectable levels of <DNA> c-jun </DNA> gene transcription in <cell_line> untreated <cell_line> HL-60 cells </cell_line> </cell_line> , and that exposure to TPA increases this rate 3.3-fold ."
  },
  {
    "input_text": "Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription .",
    "target_text": "Treatment of <cell_line> HL-60 cells </cell_line> with both TPA and cycloheximide had no effect on the rates of <DNA> c-jun </DNA> transcription ."
  },
  {
    "input_text": "The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min .",
    "target_text": "The half-life of <RNA> <DNA> c-jun </DNA> RNA </RNA> as determined by treating <cell_line> HL-60 cells </cell_line> with TPA and actinomycin D was 30 min ."
  },
  {
    "input_text": "In contrast , the half-life of c-jun RNA in TPA -treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h .",
    "target_text": "In contrast , the half-life of <RNA> <DNA> c-jun </DNA> RNA </RNA> in <cell_line> TPA -treated <cell_line> HL-60 cells </cell_line> </cell_line> exposed to cycloheximide and actinomycin D was greater than 2 h ."
  },
  {
    "input_text": "These findings suggested that the increase in c-jun RNA observed during TPA -induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms .",
    "target_text": "These findings suggested that the increase in <RNA> <DNA> c-jun </DNA> RNA </RNA> observed during TPA -induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms ."
  },
  {
    "input_text": "[ Hormonal interactions and glucocorticoid receptors in patients with the nephrotic syndrome ]",
    "target_text": "[ Hormonal interactions and <protein> glucocorticoid receptors </protein> in patients with the nephrotic syndrome ]"
  },
  {
    "input_text": "As many as 27 children aged 6 to 15 years with morphologically verified nephropathies were examined .",
    "target_text": "As many as 27 children aged 6 to 15 years with morphologically verified nephropathies were examined ."
  },
  {
    "input_text": "Four variants of changes in the thyroid status , characteristic of children with different variants of nephrotic syndrome were distinguished : 1 ) biochemical signs of primary hypothyroidism , 2 ) biochemical signs of secondary hypothyroidism , 3 ) low content of T3 , 4 ) dysfunction of the hypophyseal and thyroid system .",
    "target_text": "Four variants of changes in the thyroid status , characteristic of children with different variants of nephrotic syndrome were distinguished : 1 ) biochemical signs of primary hypothyroidism , 2 ) biochemical signs of secondary hypothyroidism , 3 ) low content of T3 , 4 ) dysfunction of the hypophyseal and thyroid system ."
  },
  {
    "input_text": "It is shown that the low level of steroid receptors , thyroid hormones that the low level of steroid receptors , thyroid hormones ( T3 and T4 ) and cortisol is typical of children with the signs of renal dysplasia .",
    "target_text": "It is shown that the low level of <protein> steroid receptors </protein> , thyroid hormones that the low level of <protein> steroid receptors </protein> , thyroid hormones ( T3 and T4 ) and cortisol is typical of children with the signs of renal dysplasia ."
  },
  {
    "input_text": "It is assumed that superaddition under such conditions of immune glomerulopathy ( glomerulonephritis and nephrotic syndrome ) gives rise to the resistance to the treatment with glucocorticoids .",
    "target_text": "It is assumed that superaddition under such conditions of immune glomerulopathy ( glomerulonephritis and nephrotic syndrome ) gives rise to the resistance to the treatment with glucocorticoids ."
  },
  {
    "input_text": "Lymphoid specific gene expression of the adenovirus early region 3 promoter is mediated by NF-kappa B binding motifs .",
    "target_text": "Lymphoid specific gene expression of the <DNA> adenovirus early region 3 promoter </DNA> is mediated by <DNA> NF-kappa B binding motifs </DNA> ."
  },
  {
    "input_text": "A primary site of infection by human adenoviruses is lymphoid cells .",
    "target_text": "A primary site of infection by human adenoviruses is <cell_type> lymphoid cells </cell_type> ."
  },
  {
    "input_text": "However , analysis of the viral control elements and the cellular factors that regulate adenoviral gene expression in lymphocytes has not been reported .",
    "target_text": "However , analysis of the <DNA> viral control elements </DNA> and the <protein> cellular factors </protein> that regulate adenoviral gene expression in <cell_type> lymphocytes </cell_type> has not been reported ."
  },
  {
    "input_text": "The adenovirus early region 3 ( ES ) gene products are involved in the maintenance of viral persistence by complexing with the class I MHC antigens , thus preventing their cell surface expression with a resultant decrease in host immunologic destruction .",
    "target_text": "The <protein> <DNA> adenovirus early region 3 </DNA> ( <DNA> ES </DNA> ) gene products </protein> are involved in the maintenance of viral persistence by complexing with the <protein> class I MHC antigens </protein> , thus preventing their cell surface expression with a resultant decrease in host immunologic destruction ."
  },
  {
    "input_text": "To determine whether different cellular factors were involved in E3 regulation in lymphocytes as compared with HeLa cells , both DNA binding and transfection analysis with the E3 promoter in both cell types were performed .",
    "target_text": "To determine whether different <protein> cellular factors </protein> were involved in E3 regulation in <cell_type> lymphocytes </cell_type> as compared with <cell_line> HeLa cells </cell_line> , both DNA binding and transfection analysis with the <DNA> E3 promoter </DNA> in both cell types were performed ."
  },
  {
    "input_text": "These studies detected two novel domains referred to as L1 and L2 with a variety of lymphoid but not HeLa extracts .",
    "target_text": "These studies detected two <DNA> novel domains </DNA> referred to as <DNA> L1 </DNA> and <DNA> L2 </DNA> with a variety of lymphoid but not HeLa extracts ."
  },
  {
    "input_text": "Each of these domains possessed strong homology to motifs previously found to bind the cellular factor NF-kappa B .",
    "target_text": "Each of these domains possessed strong homology to motifs previously found to bind the <protein> cellular factor <protein> NF-kappa B </protein> </protein> ."
  },
  {
    "input_text": "Transfections of E3 constructs linked to the chloramphenicol acetyltransferase gene revealed that mutagenesis of the distal NF-kappa B motif ( L2 ) had minimal effects on promoter expression in HeLa cells , but resulted in dramatic decreases in expression by lymphoid cells .",
    "target_text": "Transfections of <DNA> E3 constructs </DNA> linked to the <DNA> chloramphenicol acetyltransferase gene </DNA> revealed that mutagenesis of the <DNA> distal <protein> NF-kappa B </protein> motif </DNA> ( <DNA> L2 </DNA> ) had minimal effects on promoter expression in <cell_line> HeLa cells </cell_line> , but resulted in dramatic decreases in expression by <cell_type> lymphoid cells </cell_type> ."
  },
  {
    "input_text": "In contrast , mutagenesis of proximal NF-kappa B motif ( L1 ) had minimal effects on gene expression in both HeLa cells and lymphoid cells but resulted in a small , but reproducible , increase in gene expression in lymphoid cells when coupled to the L2 mutation .",
    "target_text": "In contrast , mutagenesis of <DNA> proximal NF-kappa B motif </DNA> ( <DNA> L1 </DNA> ) had minimal effects on gene expression in both <cell_line> HeLa cells </cell_line> and <cell_type> lymphoid cells </cell_type> but resulted in a small , but reproducible , increase in gene expression in <cell_type> lymphoid cells </cell_type> when coupled to the <DNA> L2 </DNA> mutation ."
  },
  {
    "input_text": "Reversing the position and subsequent mutagenesis of the L1 and L2 domains indicated that the primary sequence of these motifs rather than their position in the E3 promoter was critical for regulating gene expression .",
    "target_text": "Reversing the position and subsequent mutagenesis of the <DNA> L1 </DNA> and <DNA> <DNA> L2 </DNA> domains </DNA> indicated that the <DNA> primary sequence </DNA> of these motifs rather than their position in the <DNA> E3 promoter </DNA> was critical for regulating gene expression ."
  },
  {
    "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )",
    "target_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"
  },
  {
    "input_text": "Characterization of defensin resistance phenotypes associated with mutations in the phoP virulence regulon of Salmonella typhimurium .",
    "target_text": "Characterization of <protein> defensin </protein> resistance phenotypes associated with mutations in the <DNA> phoP virulence regulon </DNA> of Salmonella typhimurium ."
  },
  {
    "input_text": "The defensin sensitivities of Salmonella typhimurium strains with mutations in the phoP/phoQ two-component virulence regulon were tested by using purified defensins NP-1 and NP-2 .",
    "target_text": "The <protein> defensin </protein> sensitivities of Salmonella typhimurium strains with mutations in the <DNA> phoP/phoQ two-component virulence regulon </DNA> were tested by using <protein> purified defensins </protein> <protein> NP-1 </protein> and <protein> NP-2 </protein> ."
  },
  {
    "input_text": "Strains with mutations in either gene of the regulatory pair ( phoP [ transcriptional activator ] or phoQ [ membrane sensor kinase ] ) had increased sensitivities to defensin .",
    "target_text": "Strains with mutations in either gene of the <DNA> regulatory pair </DNA> ( <DNA> phoP </DNA> [ <DNA> transcriptional activator </DNA> ] or <DNA> phoQ </DNA> [ <protein> membrane sensor kinase </protein> ] ) had increased sensitivities to <protein> defensin </protein> ."
  },
  {
    "input_text": "The predicted periplasmic domain of the PhoQ protein contained a markedly anionic domain that could interact with cationic proteins and that could be responsible for resistance to defensin .",
    "target_text": "The predicted <protein> periplasmic domain </protein> of the <protein> PhoQ protein </protein> contained a markedly anionic domain that could interact with <protein> cationic proteins </protein> and that could be responsible for resistance to <protein> defensin </protein> ."
  },
  {
    "input_text": "Because insertion mutations in phoP are polar on phoQ , we constructed strains that expressed the PhoQ protein in the absence of PhoP to test whether resistance to defensin requires only the phoQ gene product .",
    "target_text": "Because insertion mutations in <DNA> phoP </DNA> are polar on <DNA> phoQ </DNA> , we constructed strains that expressed the <protein> PhoQ protein </protein> in the absence of <protein> PhoP </protein> to test whether resistance to defensin requires only the <protein> <DNA> phoQ </DNA> gene product </protein> ."
  },
  {
    "input_text": "We found that resistance to defensin requires the function of both components of this regulatory system , because strains expressing PhoQ without PhoP were still markedly sensitive to defensins .",
    "target_text": "We found that resistance to defensin requires the function of both components of this regulatory system , because strains expressing <protein> PhoQ </protein> without <protein> PhoP </protein> were still markedly sensitive to <protein> defensins </protein> ."
  },
  {
    "input_text": "This implied that a pag ( phoP -activated gene ) product is responsible for defensin resistance .",
    "target_text": "This implied that a <protein> <DNA> pag </DNA> ( <DNA> <DNA> phoP </DNA> -activated gene </DNA> ) product </protein> is responsible for <protein> defensin </protein> resistance ."
  },
  {
    "input_text": "We also tested for the ability of defensins NP-1 , NP-5 , and HNP-1 to activate pag expression and found that these peptides have no effect .",
    "target_text": "We also tested for the ability of <protein> defensins </protein> <protein> NP-1 </protein> , <protein> NP-5 </protein> , and <protein> HNP-1 </protein> to activate <DNA> pag </DNA> expression and found that these peptides have no effect ."
  },
  {
    "input_text": "Defensin resistance is not the only virulence characteristic controlled by the PhoP -PhoQ regulon because mutations in pagC , as well as ones in the phoP locus that resulted in constitutive pag activation ( phenotype PhoPc ) , had no effect on defensin resistance , even though they rendered the organism avirulent and deficient in survival within macrophages .",
    "target_text": "Defensin resistance is not the only virulence characteristic controlled by the <protein> <protein> PhoP </protein> <protein> -PhoQ </protein> regulon </protein> because mutations in <DNA> pagC </DNA> , as well as ones in the <DNA> <DNA> phoP </DNA> locus </DNA> that resulted in constitutive <DNA> pag </DNA> activation ( phenotype <protein> PhoPc </protein> ) , had no effect on <protein> defensin </protein> resistance , even though they rendered the organism avirulent and deficient in survival within <cell_type> macrophages </cell_type> ."
  },
  {
    "input_text": "The virulence defect conferred by mutations in the phoP -phoQ two-component regulatory system is not completely explained by alterations in resistance to cationic proteins and involves the control of other proteins necessary for S. typhimurium survival within macrophages .",
    "target_text": "The virulence defect conferred by mutations in the <DNA> phoP </DNA> <DNA> -phoQ </DNA> two-component regulatory system is not completely explained by alterations in resistance to <protein> cationic proteins </protein> and involves the control of other proteins necessary for S. typhimurium survival within <cell_type> macrophages </cell_type> ."
  },
  {
    "input_text": "Stimulation of a human T-cell clone with anti-CD3 or tumor necrosis factor induces NF-kappa B translocation but not human immunodeficiency virus 1 enhancer-dependent transcription .",
    "target_text": "Stimulation of a <cell_line> human T-cell clone </cell_line> with <protein> anti-CD3 </protein> or <protein> tumor necrosis factor </protein> induces <protein> NF-kappa B </protein> translocation but not human immunodeficiency virus 1 enhancer-dependent transcription ."
  },
  {
    "input_text": "The expression of transiently transfected expression vectors under the control of the long terminal repeat ( LTR ) of the human immunodeficiency virus ( HIV ) or its enhancer sequence and the translocation of the HIV enhancer-binding protein NF-kappa B were analyzed in two human T-cell clones stimulated through their T-cell receptor complex or by tumor necrosis factor or phorbol 12-myristate 13-acetate .",
    "target_text": "The expression of transiently transfected expression vectors under the control of the <DNA> long terminal repeat </DNA> ( <DNA> LTR </DNA> ) of the human immunodeficiency virus ( HIV ) or its <DNA> enhancer sequence </DNA> and the translocation of the <protein> HIV enhancer-binding protein </protein> <protein> NF-kappa B </protein> were analyzed in two human <cell_line> T-cell clones </cell_line> stimulated through their <protein> T-cell receptor complex </protein> or by <protein> tumor necrosis factor </protein> or phorbol 12-myristate 13-acetate ."
  },
  {
    "input_text": "We found a dissociation of NF-kappa B translocation from transactivation of either the HIV LTR or the HIV enhancer .",
    "target_text": "We found a dissociation of <protein> NF-kappa B </protein> translocation from transactivation of either the <DNA> HIV LTR </DNA> or the <DNA> HIV enhancer </DNA> ."
  },
  {
    "input_text": "Interleukin 2 induced proliferation but not NF-kappa B translocation or LTR transactivation .",
    "target_text": "<protein> Interleukin 2 </protein> induced proliferation but not <protein> NF-kappa B </protein> translocation or <DNA> LTR </DNA> transactivation ."
  },
  {
    "input_text": "Phorbol ester or specific antigen recognition induced HIV LTR transactivation , whereas stimulation with tumor necrosis factor or antibody to CD3 did not .",
    "target_text": "Phorbol ester or specific antigen recognition induced <DNA> HIV LTR </DNA> transactivation , whereas stimulation with <protein> tumor necrosis factor </protein> or antibody to <protein> CD3 </protein> did not ."
  },
  {
    "input_text": "The two latter signals were nevertheless able to induce NF-kappa B translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester .",
    "target_text": "The two latter signals were nevertheless able to induce <protein> NF-kappa B </protein> translocation with a pattern in the band-shift assay indistinguishable from that observed using phorbol ester ."
  },
  {
    "input_text": "Our finding that induction of NF-kappa B by tumor necrosis factor or antibody to CD3 is not sufficient to induce HIV enhancer -dependent transcription in cloned T cells contrasts with results obtained in most lymphoblastoid T-cell lines and indicates that normal T lymphocytes differ from tumoral T cells in terms of requirements for HIV LTR activation .",
    "target_text": "Our finding that induction of <protein> NF-kappa B </protein> by <protein> tumor necrosis factor </protein> or <protein> antibody to CD3 </protein> is not sufficient to induce <DNA> HIV enhancer </DNA> -dependent transcription in <cell_line> cloned T cells </cell_line> contrasts with results obtained in most <cell_line> lymphoblastoid T-cell lines </cell_line> and indicates that normal <cell_type> T <cell_type> lymphocytes </cell_type> </cell_type> differ from <cell_type> tumoral T cells </cell_type> in terms of requirements for <DNA> HIV LTR </DNA> activation ."
  },
  {
    "input_text": "Furthermore , our results suggest that events linked to T-cell activation , in addition to NF-kappa B translocation per se , induce functional interactions of the NF-kappa B complex with the HIV enhancer .",
    "target_text": "Furthermore , our results suggest that events linked to T-cell activation , in addition to <protein> NF-kappa B </protein> translocation per se , induce functional interactions of the <protein> <protein> NF-kappa B </protein> complex </protein> with the <DNA> HIV enhancer </DNA> ."
  },
  {
    "input_text": "Decreased concentration of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with X-linked hypophosphatemic rickets : effect of phosphate supplementation .",
    "target_text": "Decreased concentration of <protein> 1,25-dihydroxyvitamin D3 receptors </protein> in <cell_type> peripheral mononuclear cells </cell_type> of patients with X-linked hypophosphatemic rickets : effect of phosphate supplementation ."
  },
  {
    "input_text": "Abnormal renal tubular phosphate transport is considered to be the primary defect in X-linked hypophosphatemic rickets ( XLH ) .",
    "target_text": "Abnormal renal tubular phosphate transport is considered to be the primary defect in X-linked hypophosphatemic rickets ( XLH ) ."
  },
  {
    "input_text": "However , the resistance to vitamin D treatment in XLH can not be explained by hypophosphatemia alone .",
    "target_text": "However , the resistance to vitamin D treatment in XLH can not be explained by hypophosphatemia alone ."
  },
  {
    "input_text": "Since most of the actions of vitamin D are mediated by its receptors ( VDR ) , abnormalities of VDR have been postulated in XLH .",
    "target_text": "Since most of the actions of vitamin D are mediated by its receptors ( <protein> VDR </protein> ) , abnormalities of <protein> VDR </protein> have been postulated in XLH ."
  },
  {
    "input_text": "In order to investigate this possibility , we measured the concentration of VDR in PHA-activated peripheral mononuclear cells from 10 XLH patients .",
    "target_text": "In order to investigate this possibility , we measured the concentration of <protein> VDR </protein> in <cell_line> PHA-activated <cell_type> peripheral mononuclear cells </cell_type> </cell_line> from 10 XLH patients ."
  },
  {
    "input_text": "Patients without phosphate supplementation showed significantly lower concentration ( 21.7 +/- 5.1 fmol/mg protein , mean +/- SEM ) compared to the normal controls ( 60.7 +/- 4.0 ) .",
    "target_text": "Patients without phosphate supplementation showed significantly lower concentration ( 21.7 +/- 5.1 fmol/mg protein , mean +/- SEM ) compared to the normal controls ( 60.7 +/- 4.0 ) ."
  },
  {
    "input_text": "On the contrary , there was no significant difference between the phosphate-supplemented patients ( 58.3 +/- 2.7 ) and controls .",
    "target_text": "On the contrary , there was no significant difference between the phosphate-supplemented patients ( 58.3 +/- 2.7 ) and controls ."
  },
  {
    "input_text": "There was a significant positive correlation between VDR concentration and serum phosphate ( P less than 0.05 ) .",
    "target_text": "There was a significant positive correlation between <protein> VDR </protein> concentration and serum phosphate ( P less than 0.05 ) ."
  },
  {
    "input_text": "In two patients , VDR was increased after daily phosphate supplementation was started .",
    "target_text": "In two patients , <protein> VDR </protein> was increased after daily phosphate supplementation was started ."
  },
  {
    "input_text": "These results indicate that a decreased concentration of VDR secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH .",
    "target_text": "These results indicate that a decreased concentration of <protein> VDR </protein> secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH ."
  },
  {
    "input_text": "Two distinct forms of active transcription factor CREB ( cAMP response element binding protein ) .",
    "target_text": "Two distinct forms of <protein> active transcription factor CREB </protein> ( <protein> cAMP response element binding protein </protein> ) ."
  },
  {
    "input_text": "Mammalian cells express two distinct forms of transcription factor CREB ( cAMP response element binding protein ) that are apparently the products of alternative splicing of the CREB gene transcript .",
    "target_text": "<cell_type> Mammalian cells </cell_type> express two distinct forms of <protein> transcription factor <protein> CREB </protein> </protein> ( <protein> cAMP response element binding protein </protein> ) that are apparently the products of alternative splicing of the <RNA> <protein> CREB </protein> gene transcript </RNA> ."
  },
  {
    "input_text": "The two proteins differ by a 14-amino acid serine-rich insertion present in one of the CREB isoforms .",
    "target_text": "The two proteins differ by a <protein> 14-amino acid serine-rich insertion </protein> present in one of the <protein> <protein> CREB </protein> isoforms </protein> ."
  },
  {
    "input_text": "We show that both CREB isoforms are expressed in many cell types and mammalian species .",
    "target_text": "We show that both <protein> <protein> CREB </protein> isoforms </protein> are expressed in <cell_type> many cell types </cell_type> and mammalian species ."
  },
  {
    "input_text": "Both encode proteins that bind specifically to a cAMP response element in vitro .",
    "target_text": "Both encode proteins that bind specifically to a <DNA> cAMP response element in vitro </DNA> ."
  },
  {
    "input_text": "As expected for proteins of this class , the CREB proteins bind DNA as dimers .",
    "target_text": "As expected for proteins of this class , the <protein> <protein> CREB </protein> proteins </protein> bind DNA as dimers ."
  },
  {
    "input_text": "Both proteins impart cAMP -regulated transcriptional activity to a heterologous DNA-binding domain , showing that cAMP directly modulates the transcriptional stimulatory activity of CREB .",
    "target_text": "Both proteins impart cAMP -regulated transcriptional activity to a <DNA> heterologous DNA-binding domain </DNA> , showing that cAMP directly modulates the transcriptional stimulatory activity of <protein> CREB </protein> ."
  },
  {
    "input_text": "The presence of multiple CREB isoforms with identical DNA-binding specificities but differences in the presumed regulatory domain raises the possibility that CREB proteins may be able to integrate distinct regulatory signals at the level of gene transcription .",
    "target_text": "The presence of multiple <protein> <protein> CREB </protein> isoforms </protein> with identical DNA-binding specificities but differences in the presumed <protein> regulatory domain </protein> raises the possibility that <protein> <protein> CREB </protein> proteins </protein> may be able to integrate distinct regulatory signals at the level of gene transcription ."
  },
  {
    "input_text": "Human immunodeficiency virus vpr product is a virion-associated regulatory protein .",
    "target_text": "<protein> Human immunodeficiency virus vpr product </protein> is a <protein> virion-associated regulatory protein </protein> ."
  },
  {
    "input_text": "The vpr product of the human immunodeficiency virus type 1 ( HIV-1 ) acts in trans to accelerate virus replication and cytopathic effect in T cells .",
    "target_text": "The <protein> vpr product </protein> of the human immunodeficiency virus type 1 ( HIV-1 ) acts in trans to accelerate virus replication and cytopathic effect in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "Here it is shown that the HIV-1 viral particle contains multiple copies of the vpr protein .",
    "target_text": "Here it is shown that the HIV-1 viral particle contains multiple copies of the <protein> vpr protein </protein> ."
  },
  {
    "input_text": "The vpr product is the first regulatory protein of HIV-1 to be found in the virus particle .",
    "target_text": "The <protein> vpr product </protein> is the first regulatory protein of HIV-1 to be found in the virus particle ."
  },
  {
    "input_text": "This observation raises the possibility that vpr acts to facilitate the early steps of infection before de novo viral protein synthesis occurs .",
    "target_text": "This observation raises the possibility that <DNA> vpr </DNA> acts to facilitate the early steps of infection before de novo viral protein synthesis occurs ."
  },
  {
    "input_text": "A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation .",
    "target_text": "A novel <protein> B-cell lineage-specific transcription factor </protein> present at early but not late stages of <protein> differentiation </protein> ."
  },
  {
    "input_text": "A novel B-cell-specific transcription factor , BSAP , was identified as a mammalian homolog of the sea urchin protein TSAP , which interacts with the promoters of four tissue-specific late histone H2A-2 and H2B-2 genes .",
    "target_text": "A novel <protein> B-cell-specific transcription factor </protein> , <protein> BSAP </protein> , was identified as a <protein> mammalian homolog </protein> of the <protein> sea urchin protein </protein> <protein> TSAP </protein> , which interacts with the <DNA> promoters </DNA> of four tissue-specific late histone H2A-2 and H2B-2 genes ."
  },
  {
    "input_text": "As shown by mobility-shift , methylation interference , and mutational analyses , the mammalian protein BSAP recognizes all four sea urchin binding sites in a manner indistinguishable from TSAP ; however , the two proteins differ in molecular weight .",
    "target_text": "As shown by mobility-shift , methylation interference , and mutational analyses , the <protein> mammalian protein </protein> <protein> BSAP </protein> recognizes all four <DNA> sea urchin binding sites </DNA> in a manner indistinguishable from <protein> TSAP </protein> ; however , the two proteins differ in molecular weight ."
  },
  {
    "input_text": "BSAP is exclusively restricted to the B-cell lineage of lymphoid differentiation .",
    "target_text": "<protein> BSAP </protein> is exclusively restricted to the B-cell lineage of lymphoid differentiation ."
  },
  {
    "input_text": "Its expression appears to be activated during pro-B-cell development , is abundant at the pre-B- and mature B- cell stages , but is absent in terminally differentiated plasma cells .",
    "target_text": "Its expression appears to be activated during pro-B-cell development , is abundant at the pre-B- and mature B- cell stages , but is absent in <cell_type> terminally differentiated plasma cells </cell_type> ."
  },
  {
    "input_text": "Moreover , BSAP is clearly a B-cell-specific transcription factor , as a wild-type but not a mutant TSAP -binding site of the sea urchin functions only in transfected B cells as an upstream promoter element .",
    "target_text": "Moreover , <protein> BSAP </protein> is clearly a <protein> B-cell-specific transcription factor </protein> , as a <DNA> wild-type </DNA> but not a <DNA> mutant <protein> TSAP </protein> -binding site </DNA> of the sea urchin functions only in <cell_line> transfected B cells </cell_line> as an <DNA> upstream promoter element </DNA> ."
  },
  {
    "input_text": "Competition experiments did not reveal any high-affinity binding site for BSAP in known regulatory regions of immunoglobulin and class II major histocompatibility ( MHC ) genes , suggesting that BSAP is a regulator of a different set of B-lymphoid-specific genes .",
    "target_text": "Competition experiments did not reveal any <DNA> high-affinity binding site </DNA> for <protein> BSAP </protein> in known <DNA> regulatory regions </DNA> of immunoglobulin and class II major histocompatibility ( MHC ) genes , suggesting that <protein> BSAP </protein> is a regulator of a different set of <DNA> B-lymphoid-specific genes </DNA> ."
  },
  {
    "input_text": "Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression .",
    "target_text": "<protein> Octamer transcription factors </protein> and the <DNA> cell type-specificity of immunoglobulin gene </DNA> expression ."
  },
  {
    "input_text": "Antibodies are produced exclusively in B lymphocytes .",
    "target_text": "<protein> Antibodies </protein> are produced exclusively in <cell_type> B <cell_type> lymphocytes </cell_type> </cell_type> ."
  },
  {
    "input_text": "The expression of the antibody-encoding genes , the immunoglobulin ( Ig ) genes , is also restricted to B cells .",
    "target_text": "The expression of the <DNA> antibody-encoding genes </DNA> , the <DNA> immunoglobulin ( Ig ) genes </DNA> , is also restricted to <cell_type> B cells </cell_type> ."
  },
  {
    "input_text": "The octamer sequence ATGCAAAT is present in the promoter and the enhancer of Ig genes , and plays an important role in its tissue-specific expression .",
    "target_text": "The <DNA> octamer sequence </DNA> ATGCAAAT is present in the <DNA> promoter </DNA> and the <DNA> enhancer </DNA> of <DNA> Ig genes </DNA> , and plays an important role in its tissue-specific expression ."
  },
  {
    "input_text": "This sequence motif is a binding site for nuclear proteins , the so-called octamer transcription factors ( Oct or OTF factors ) .",
    "target_text": "This <DNA> sequence motif </DNA> is a binding site for <protein> nuclear proteins </protein> , the so-called <protein> octamer transcription factors </protein> ( <protein> Oct </protein> or <protein> OTF factors </protein> ) ."
  },
  {
    "input_text": "The Oct-1 protein is present in all cell types analyzed so far , whereas Oct-2A and Oct-2B are found mainly in B lymphocytes .",
    "target_text": "The <protein> Oct-1 protein </protein> is present in all cell types analyzed so far , whereas <protein> Oct-2A </protein> and <protein> Oct-2B </protein> are found mainly in <cell_type> B <cell_type> lymphocytes </cell_type> </cell_type> ."
  },
  {
    "input_text": "All three proteins show the same sequence specificity and binding affinity .",
    "target_text": "All three proteins show the same sequence specificity and binding affinity ."
  },
  {
    "input_text": "It appears that the B cell-specific expression of Ig genes is mediated at least in part by cell type-specific Oct factors , and that there are both quantitative and qualitative differences between Oct-1 and Oct-2 factors .",
    "target_text": "It appears that the B cell-specific expression of <DNA> Ig genes </DNA> is mediated at least in part by cell <protein> type-specific Oct factors </protein> , and that there are both quantitative and qualitative differences between <protein> Oct-1 </protein> and <protein> Oct-2 factors </protein> ."
  },
  {
    "input_text": "Recently , a number of other octamer factor variants were identified .",
    "target_text": "Recently , a number of other <protein> octamer factor variants </protein> were identified ."
  },
  {
    "input_text": "Many of these may be created by alternative splicing of a primary transcript of one Oct factor gene and may serve a specific function in the fine tuning of gene expression .",
    "target_text": "Many of these may be created by alternative splicing of a <RNA> primary transcript </RNA> of one Oct factor gene and may serve a specific function in the fine tuning of gene expression ."
  },
  {
    "input_text": "A factor known to bind to endogenous Ig heavy chain enhancer only in lymphocytes is a ubiquitously active transcription factor .",
    "target_text": "A factor known to bind to <DNA> endogenous Ig heavy chain enhancer </DNA> only in <cell_type> lymphocytes </cell_type> is a <protein> ubiquitously active transcription factor </protein> ."
  },
  {
    "input_text": "The transcriptional enhancer located in the first intron of the immunoglobulin heavy chain constant region is a major determinant of B-cell-specific expression of immunoglobulin genes .",
    "target_text": "The <DNA> transcriptional enhancer </DNA> located in the first intron of the <DNA> immunoglobulin heavy chain constant region </DNA> is a major determinant of B-cell-specific expression of <DNA> immunoglobulin genes </DNA> ."
  },
  {
    "input_text": "Like other enhancers , the Ig heavy chain enhancer contains several short sequence motifs that bind specific transcription factors .",
    "target_text": "Like other <DNA> enhancers </DNA> , the <DNA> Ig heavy chain enhancer </DNA> contains several short <DNA> sequence motifs </DNA> that bind <protein> specific transcription factors </protein> ."
  },
  {
    "input_text": "Each binding site contributes to the overall activity of the enhancer , however no single element seems absolutely required for activity .",
    "target_text": "Each <DNA> binding site </DNA> contributes to the overall activity of the <DNA> enhancer </DNA> , however no single element seems absolutely required for activity ."
  },
  {
    "input_text": "For a better understanding of the Ig heavy chain enhancer components , we have cloned and analyzed individual sequence elements .",
    "target_text": "For a better understanding of the <DNA> <DNA> Ig heavy chain enhancer </DNA> components </DNA> , we have cloned and analyzed individual <DNA> sequence elements </DNA> ."
  },
  {
    "input_text": "We find that the factor that binds to the E3 enhancer motif , CATGTGGC , is a ubiquitous transcription factor .",
    "target_text": "We find that the factor that binds to the <DNA> E3 enhancer motif </DNA> , CATGTGGC , is a <protein> ubiquitous transcription factor </protein> ."
  },
  {
    "input_text": "It is present in an active form in both B cells and non- B cells , where it can mediate transcriptional activation in vitro and in vivo .",
    "target_text": "It is present in an active form in both <cell_type> B cells </cell_type> and <cell_type> non- <cell_type> B cells </cell_type> </cell_type> , where it can mediate transcriptional activation in vitro and in vivo ."
  },
  {
    "input_text": "However , despite its ability to activate transcription of a transfected reporter gene , the factor is apparently unable to bind to the endogenous Ig heavy chain enhancer in non- lymphoid cells : In previous experiments by others , the characteristic in vivo footprint of this factor , designated NF-muE3 , was detected in B cells but not in non-B cells .",
    "target_text": "However , despite its ability to activate transcription of a <DNA> transfected reporter gene </DNA> , the factor is apparently unable to bind to the <DNA> endogenous <DNA> Ig heavy chain enhancer </DNA> </DNA> in <cell_type> non- <cell_type> lymphoid cells </cell_type> </cell_type> : In previous experiments by others , the characteristic in vivo footprint of this factor , designated <protein> NF-muE3 </protein> , was detected in <cell_type> B cells </cell_type> but not in <cell_type> non-B cells </cell_type> ."
  },
  {
    "input_text": "From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in B lymphocytes : ( a ) cell-specific factors such as Oct-2A and Oct-2B that are not expressed in most other cell types : ( b ) ubiquitous factors such as NF-kappa B that are constitutively active in B cells but are sequestered in an inactive form in other cells ; ( c ) ubiquitously active factors , exemplified by the one binding to the E3 sequence motif .",
    "target_text": "From this and other findings the picture emerges that there are at least three categories of factors which mediate cell-type-specific transcription in <cell_type> B <cell_type> lymphocytes </cell_type> </cell_type> : ( a ) <protein> cell-specific factors </protein> such as <protein> Oct-2A </protein> and <protein> Oct-2B </protein> that are not expressed in most other cell types : ( b ) <protein> ubiquitous factors </protein> such as <protein> NF-kappa B </protein> that are constitutively active in <cell_type> B cells </cell_type> but are sequestered in an inactive form in other cells ; ( c ) <protein> ubiquitously active factors </protein> , exemplified by the one binding to the <DNA> E3 sequence motif </DNA> ."
  },
  {
    "input_text": "This factor is present in an active form in a variety of cell types but is apparently unable to bind to the endogenous Ig heavy chain enhancer in non-B cells , perhaps due to a non-permissive chromatin structure of the Ig heavy chain locus .",
    "target_text": "This factor is present in an active form in a variety of cell types but is apparently unable to bind to the <DNA> endogenous <DNA> Ig heavy chain enhancer </DNA> </DNA> in <cell_type> non-B cells </cell_type> , perhaps due to a non-permissive <DNA> chromatin </DNA> structure of the <DNA> Ig heavy chain locus </DNA> ."
  },
  {
    "input_text": "[ Endocrine status changes in children with bronchial asthma ]",
    "target_text": "[ Endocrine status changes in children with bronchial asthma ]"
  },
  {
    "input_text": "A study was made of adrenocortical function by measuring blood plasma cortisol concentration and amount of glucocorticoid receptors in lymphocytes as well as thyroid function by measuring blood plasma triidothyronine and thyroxine concentration in 58 bronchial asthma children aged 1 to 14 years .",
    "target_text": "A study was made of adrenocortical function by measuring blood plasma cortisol concentration and amount of <protein> glucocorticoid receptors </protein> in <cell_type> lymphocytes </cell_type> as well as thyroid function by measuring blood plasma triidothyronine and thyroxine concentration in 58 bronchial asthma children aged 1 to 14 years ."
  },
  {
    "input_text": "The authors revealed alterations in the functional activity of the indicated endocrine glands depending on the intensity of bronchial patency disorders and the nature of the therapeutic measures carried out .",
    "target_text": "The authors revealed alterations in the functional activity of the indicated endocrine glands depending on the intensity of bronchial patency disorders and the nature of the therapeutic measures carried out ."
  },
  {
    "input_text": "TAR independent activation of the human immunodeficiency virus in phorbol ester stimulated T lymphocytes .",
    "target_text": "<DNA> TAR </DNA> independent activation of the human immunodeficiency virus in phorbol ester stimulated <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "Multiple regulatory elements in the human immunodeficiency virus long terminal repeat ( HIV LTR ) are required for activation of HIV gene expression .",
    "target_text": "<DNA> Multiple regulatory elements </DNA> in the <DNA> human immunodeficiency virus <DNA> long terminal repeat </DNA> </DNA> ( <DNA> HIV LTR </DNA> ) are required for activation of HIV gene expression ."
  },
  {
    "input_text": "Previous transfection studies of HIV LTR constructs linked to the chloramphenicol acetyltransferase gene indicated that multiple regulatory regions including the enhancer , SP1 , TATA and TAR regions were important for HIV gene expression .",
    "target_text": "Previous transfection studies of <DNA> <DNA> HIV LTR </DNA> constructs </DNA> linked to the <DNA> chloramphenicol acetyltransferase gene </DNA> indicated that multiple <DNA> regulatory regions </DNA> including the <DNA> enhancer </DNA> , <DNA> SP1 </DNA> , <DNA> TATA </DNA> and <DNA> TAR regions </DNA> were important for HIV gene expression ."
  },
  {
    "input_text": "To characterize these regulatory elements further , mutations in these regions were inserted into both the 5' and 3' HIV LTRs and infectious proviral constructs were assembled .",
    "target_text": "To characterize these <DNA> regulatory elements </DNA> further , mutations in these regions were inserted into both the 5' and 3' <DNA> HIV LTRs </DNA> and infectious proviral constructs were assembled ."
  },
  {
    "input_text": "These constructs were transfected into either HeLa cells , Jurkat cells or U937 cells in both the presence and absence of phorbol esters which have previously been demonstrated to activate HIV gene expression .",
    "target_text": "These constructs were transfected into either <cell_line> HeLa cells </cell_line> , <cell_line> Jurkat cells </cell_line> or <cell_line> U937 cells </cell_line> in both the presence and absence of phorbol esters which have previously been demonstrated to activate HIV gene expression ."
  },
  {
    "input_text": "Viral gene expression was assayed by the level of p24 gag protein released from cultures transfected with the proviral constructs .",
    "target_text": "Viral gene expression was assayed by the level of <protein> p24 gag protein </protein> released from cultures transfected with the proviral constructs ."
  },
  {
    "input_text": "Results in all cell lines indicated that mutations of the SP1 , TATA and the TAR loop and stem secondary structure resulted in marked decreases in gene expression while mutations of the enhancer motif or TAR primary sequence resulted in only slight decreases .",
    "target_text": "Results in all cell lines indicated that mutations of the <DNA> SP1 </DNA> , <DNA> TATA </DNA> and the <DNA> TAR loop </DNA> and <DNA> stem secondary structure </DNA> resulted in marked decreases in gene expression while mutations of the <DNA> enhancer motif </DNA> or <DNA> TAR primary sequence </DNA> resulted in only slight decreases ."
  },
  {
    "input_text": "However , viruses containing mutations in either the TAR loop sequences or stem secondary structure which were very defective for gene expression in untreated Jurkat cells , gave nearly wild-type levels of gene expression in phorbol ester -treated Jurkat cells but not in phorbol ester -treated HeLa or U937 cells .",
    "target_text": "However , viruses containing mutations in either the <DNA> TAR loop sequences </DNA> or <DNA> stem secondary structure </DNA> which were very defective for gene expression in untreated <cell_line> Jurkat cells </cell_line> , gave nearly wild-type levels of gene expression in <cell_line> phorbol ester -treated <cell_line> Jurkat cells </cell_line> </cell_line> but not in <cell_line> phorbol ester -treated HeLa </cell_line> or <cell_line> U937 cells </cell_line> ."
  },
  {
    "input_text": "High level gene expression of these TAR mutant constructs in phorbol ester -treated Jurkat cells was eliminated by second site mutations in the enhancer region or by disruption of the tat gene .",
    "target_text": "High level gene expression of these <DNA> TAR mutant constructs </DNA> in <cell_line> phorbol ester -treated <cell_line> Jurkat cells </cell_line> </cell_line> was eliminated by second site mutations in the <DNA> enhancer region </DNA> or by disruption of the <DNA> tat gene </DNA> ."
  },
  {
    "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )",
    "target_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"
  },
  {
    "input_text": "A case of hypersensitivity to thyroid hormones with normally functioning thyroid gland and increased nuclear triiodothyronine receptors .",
    "target_text": "A case of hypersensitivity to thyroid hormones with normally functioning thyroid gland and increased nuclear <protein> triiodothyronine receptors </protein> ."
  },
  {
    "input_text": "A 52-year-old male presented himself with tachycardia crises which appeared first during childhood , increased in frequency without goiter or exophthalmos .",
    "target_text": "A 52-year-old male presented himself with tachycardia crises which appeared first during childhood , increased in frequency without goiter or exophthalmos ."
  },
  {
    "input_text": "Cardiac and adrenergic diseases were excluded .",
    "target_text": "Cardiac and adrenergic diseases were excluded ."
  },
  {
    "input_text": "The thyroid function was normal regarding T4 , free T4 and T3 , TBG , radioiodine uptake , TSH and T3 suppressibility ; however the TSH response to TRH was decreased .",
    "target_text": "The thyroid function was normal regarding T4 , free T4 and T3 , TBG , radioiodine uptake , TSH and T3 suppressibility ; however the TSH response to TRH was decreased ."
  },
  {
    "input_text": "The lymphocyte nuclear T3 receptor was found with an affinity close to that of normal volunteers ( Ka : 1.42 x 10(10) M-1 vs 1.95 +/- 0.35 x 10(10) M-1 ) and a binding capacity markedly increased ( 9.9 vs 3.7 +/- 0.4 fmol T3 / 100 micrograms DNA ) .",
    "target_text": "The <protein> lymphocyte nuclear T3 receptor </protein> was found with an affinity close to that of normal volunteers ( Ka : 1.42 x 10(10) M-1 vs 1.95 +/- 0.35 x 10(10) M-1 ) and a binding capacity markedly increased ( 9.9 vs 3.7 +/- 0.4 fmol T3 / 100 micrograms DNA ) ."
  },
  {
    "input_text": "Pindolol was inefficient on the dysrhythmia which disappeared with carbimazole and relapsed after withdrawal of the antithyroid drug .",
    "target_text": "Pindolol was inefficient on the dysrhythmia which disappeared with carbimazole and relapsed after withdrawal of the antithyroid drug ."
  },
  {
    "input_text": "Under carbimazole , the plasma T4 markedly decreased ( 27.7 +/- 3.6 nmol/l ) but the patient remained euthyroid .",
    "target_text": "Under carbimazole , the plasma T4 markedly decreased ( 27.7 +/- 3.6 nmol/l ) but the patient remained euthyroid ."
  },
  {
    "input_text": "The clinical course and the laboratory data suggest that the tachycardia crises are the consequence of a hypersensitivity of the heart to thyroid hormones , associated with an increased number of T3 nuclear receptor sites in lymphocytes .",
    "target_text": "The clinical course and the laboratory data suggest that the tachycardia crises are the consequence of a hypersensitivity of the heart to thyroid hormones , associated with an increased number of <protein> T3 nuclear receptor </protein> sites in <cell_type> lymphocytes </cell_type> ."
  },
  {
    "input_text": "Induction of immediate early response genes by macrophage colony-stimulating factor in normal human monocytes .",
    "target_text": "Induction of <DNA> immediate early response genes </DNA> by <protein> macrophage colony-stimulating factor </protein> in <cell_type> normal human monocytes </cell_type> ."
  },
  {
    "input_text": "A group of coordinately induced protooncogenes , cytoskeletal , and extracellular matrix genes have been termed immediate early response genes , and their induction has been associated with growth factor -stimulated cell proliferation .",
    "target_text": "A group of coordinately induced <DNA> protooncogenes </DNA> , cytoskeletal , and extracellular matrix genes have been termed <DNA> immediate early response genes </DNA> , and their induction has been associated with <protein> growth factor </protein> -stimulated cell proliferation ."
  },
  {
    "input_text": "We have investigated the induction of these genes by macrophage-CSF ( M-CSF ) in human monocytes that do not proliferate in response to M-CSF but require the factor for optimal cell differentiation .",
    "target_text": "We have investigated the induction of these genes by <protein> macrophage-CSF </protein> ( <protein> M-CSF </protein> ) in <cell_type> human monocytes </cell_type> that do not proliferate in response to <protein> M-CSF </protein> but require the factor for optimal cell differentiation ."
  },
  {
    "input_text": "Normal human monocytes were isolated , carefully washed , and incubated for 36 to 48 h in fetal bovine serum-containing medium .",
    "target_text": "Normal <cell_type> human monocytes </cell_type> were isolated , carefully washed , and incubated for 36 to 48 h in fetal bovine serum-containing medium ."
  },
  {
    "input_text": "At the end of this incubation the resting cells were stimulated with M-CSF , and RNA was isolated for analysis by Northern blotting .",
    "target_text": "At the end of this incubation the <cell_type> resting cells </cell_type> were stimulated with <protein> M-CSF </protein> , and <RNA> RNA </RNA> was isolated for analysis by Northern blotting ."
  },
  {
    "input_text": "RNA from control resting cells contained low to undetectable levels of c-jun , fibronectin receptor , and actin mRNA .",
    "target_text": "<RNA> RNA </RNA> from control <cell_type> resting cells </cell_type> contained low to undetectable levels of <RNA> c-jun </RNA> , <RNA> fibronectin receptor </RNA> , and <RNA> actin mRNA </RNA> ."
  },
  {
    "input_text": "Within 15 to 30 min of addition of M-CSF , however , there was a dramatic coordinate induction of these genes .",
    "target_text": "Within 15 to 30 min of addition of <protein> M-CSF </protein> , however , there was a dramatic coordinate induction of these genes ."
  },
  {
    "input_text": "The c-jun gene expression was very transient and was not detectable by 60 min after M-CSF addition .",
    "target_text": "The <DNA> c-jun gene </DNA> expression was very transient and was not detectable by 60 min after <protein> M-CSF </protein> addition ."
  },
  {
    "input_text": "In contrast , the expression of actin and fibronectin receptor mRNA was more sustained , and the expression of these genes remained elevated at 24 to 48 h after M-CSF addition .",
    "target_text": "In contrast , the expression of actin and fibronectin receptor mRNA was more sustained , and the expression of these genes remained elevated at 24 to 48 h after <protein> M-CSF </protein> addition ."
  },
  {
    "input_text": "We also observed the induction of the myelomonocytic specific tyrosine kinase hck gene simultaneously with the other immediate early response genes .",
    "target_text": "We also observed the induction of the <DNA> <protein> myelomonocytic specific tyrosine kinase </protein> hck gene </DNA> simultaneously with the other <DNA> immediate early response genes </DNA> ."
  },
  {
    "input_text": "The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes , and in fact , super-induced the expression of c-jun and hck .",
    "target_text": "The protein synthesis inhibitor cycloheximide did not block the induction of any of these genes , and in fact , super-induced the expression of <DNA> c-jun </DNA> and <DNA> hck </DNA> ."
  },
  {
    "input_text": "Nuclear run on transcription of the c-jun , hck , and actin genes .",
    "target_text": "Nuclear run on transcription of the <DNA> c-jun </DNA> , <DNA> hck </DNA> , and <DNA> actin genes </DNA> ."
  },
  {
    "input_text": "Therefore , in normal human monocytes M-CSF induces immediate early response genes without inducing cell proliferation .",
    "target_text": "Therefore , in <cell_type> normal <cell_type> human monocytes </cell_type> </cell_type> <protein> M-CSF </protein> induces <DNA> immediate early response genes </DNA> without inducing cell proliferation ."
  },
  {
    "input_text": "These genes may then play a role in altering the physiologic status of the cells in response to CSF .",
    "target_text": "These genes may then play a role in altering the physiologic status of the cells in response to <protein> CSF </protein> ."
  },
  {
    "input_text": "Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner .",
    "target_text": "Inducible <protein> nuclear factor </protein> binding to the <DNA> kappa B elements </DNA> of the <DNA> human immunodeficiency virus enhancer </DNA> in <cell_type> T cells </cell_type> can be blocked by cyclosporin A in a signal-dependent manner ."
  },
  {
    "input_text": "Cyclosporin A ( CsA ) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation , among them the gene coding for interleukin-2 .",
    "target_text": "Cyclosporin A ( CsA ) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of <DNA> lymphokine genes </DNA> which are induced upon T-cell activation , among them the gene coding for <protein> interleukin-2 </protein> ."
  },
  {
    "input_text": "In addition , the activation of the human immunodeficiency virus ( HIV ) is partially suppressed .",
    "target_text": "In addition , the activation of the human immunodeficiency virus ( HIV ) is partially suppressed ."
  },
  {
    "input_text": "To better understand the molecular mechanisms underlying suppression by CsA , we have investigated the effects of this drug on transcription factors in T cells .",
    "target_text": "To better understand the molecular mechanisms underlying suppression by CsA , we have investigated the effects of this drug on <protein> transcription factors </protein> in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "Here we report that the formation of two distinct mitogen-inducible DNA-binding complexes , the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer , is inhibited in the presence of CsA .",
    "target_text": "Here we report that the formation of two distinct <protein> mitogen-inducible DNA-binding complexes </protein> , the <protein> kappa B complex </protein> within the <DNA> HIV enhancer </DNA> and the <protein> NFAT-1 complex </protein> within the <DNA> <protein> interleukin-2 </protein> enhancer </DNA> , is inhibited in the presence of CsA ."
  },
  {
    "input_text": "The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate -mediated activation is completely insensitive to the drug .",
    "target_text": "The kappa B-binding activity with the <DNA> HIV enhancer </DNA> is inhibited only if it is activated via the <protein> mitogen </protein> <protein> phytohemagglutinin </protein> whereas phorbol myristate acetate -mediated activation is completely insensitive to the drug ."
  },
  {
    "input_text": "This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA .",
    "target_text": "This suggests a model in which functionally indistinguishable <protein> kappa B complexes </protein> can be activated via two separate pathways of signal transduction distinguishable by CsA ."
  },
  {
    "input_text": "Purification of TCF-1 alpha , a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner .",
    "target_text": "Purification of <protein> TCF-1 alpha </protein> , a <protein> T-cell-specific transcription factor </protein> that activates the <DNA> T-cell receptor C alpha gene enhancer </DNA> in a context-dependent manner ."
  },
  {
    "input_text": "The differentiation of T cells into functionally diverse subpopulations is controlled in part , by transcriptional activation and silencing ; however , little is known in detail about the proteins that influence this developmental process .",
    "target_text": "The differentiation of <cell_type> T cells </cell_type> into functionally diverse subpopulations is controlled in part , by transcriptional activation and silencing ; however , little is known in detail about the proteins that influence this developmental process ."
  },
  {
    "input_text": "We have purified a new T-cell-specific factor , TCF-1 alpha , that is implicated in the activation of genes encoding a major component of the human T-cell receptor ( TCR ) .",
    "target_text": "We have purified a new <protein> T-cell-specific factor </protein> , <protein> TCF-1 alpha </protein> , that is implicated in the activation of genes encoding a major component of the <protein> human T-cell receptor </protein> ( <protein> TCR </protein> ) ."
  },
  {
    "input_text": "TCF-1 alpha , originally identified and purified through its binding sites on the HIV-1 promoter , was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene ( e.g. , p56lck and CD3 delta ) .",
    "target_text": "<protein> TCF-1 alpha </protein> , originally identified and purified through its binding sites on the <DNA> HIV-1 promoter </DNA> , was found to bind to the <DNA> <protein> TCR </protein> alpha enhancer </DNA> and to <DNA> promoters </DNA> for several <DNA> genes </DNA> expressed at significantly earlier stages of T-cell development than the <DNA> <protein> TCR </protein> alpha gene </DNA> ( e.g. , <DNA> p56lck </DNA> and <DNA> CD3 delta </DNA> ) ."
  },
  {
    "input_text": "Sequences related to the TCF-1 alpha binding motif ( 5'-GGCACCCTTTGA-3' ) are also found in the human TCR delta ( and possibly TCR beta ) enhancers .",
    "target_text": "Sequences related to the <DNA> <protein> TCF-1 alpha </protein> binding motif </DNA> ( 5'-GGCACCCTTTGA-3' ) are also found in the <DNA> human <DNA> <protein> TCR </protein> delta </DNA> </DNA> ( and possibly <DNA> <protein> TCR </protein> beta </DNA> ) <DNA> enhancers </DNA> ."
  },
  {
    "input_text": "Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines ( Jurkat , CCRF-CEM ) and not in mature B cells ( JY , Namalwa ) or nonlymphoid ( HeLa ) cell lines .",
    "target_text": "Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that <protein> TCF-1 alpha </protein> activity is derived from a family of <protein> 57- to 53-kD proteins </protein> that are abundantly expressed in mature and immature T-cell lines ( <cell_line> Jurkat </cell_line> , <cell_line> CCRF-CEM </cell_line> ) and not in <cell_line> mature B cells </cell_line> ( <cell_line> JY </cell_line> , <cell_line> Namalwa </cell_line> ) or <cell_line> nonlymphoid ( HeLa ) cell lines </cell_line> ."
  },
  {
    "input_text": "A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element ( the CRE or T alpha 1 motif ) and the binding site for a distinct lymphoid-specific protein ( TCF-2 alpha ) behaved as a potent T-cell-specific enhancer in vivo .",
    "target_text": "A small 95-bp fragment of the <DNA> <protein> TCR </protein> alpha control region </DNA> that contains the <DNA> <protein> TCF-1 alpha </protein> binding site </DNA> juxtaposed between a <DNA> cAMP-response element </DNA> ( the <DNA> CRE </DNA> or <DNA> T alpha 1 motif </DNA> ) and the <DNA> binding site </DNA> for a distinct <protein> lymphoid-specific protein </protein> ( <protein> TCF-2 alpha </protein> ) behaved as a potent <DNA> T-cell-specific enhancer </DNA> in vivo ."
  },
  {
    "input_text": "Tandem copies of this enhancer functioned synergistically in mature ( Jurkat ) T-cell lines as well as resting and activated immature ( CCRF-CEM ) T-cell lines .",
    "target_text": "Tandem copies of this enhancer functioned synergistically in <cell_line> mature ( Jurkat ) T-cell lines </cell_line> as well as resting and activated <cell_line> immature ( CCRF-CEM ) T-cell lines </cell_line> ."
  },
  {
    "input_text": "Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats .",
    "target_text": "Mutation of the <DNA> <protein> TCF-1 alpha </protein> binding site </DNA> diminished enhancer activity and disrupted the synergism observed in vivo between <DNA> tandem enhancer repeats </DNA> ."
  },
  {
    "input_text": "The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells , confirming that TCF-1 alpha is a T-cell-specific transcription factor .",
    "target_text": "The <DNA> <protein> TCF-1 alpha </protein> binding site </DNA> was also required for <protein> TCR </protein> alpha enhancer activity in transcriptionally active extracts from <cell_line> Jurkat </cell_line> but not <cell_line> HeLa cells </cell_line> , confirming that <protein> TCF-1 alpha </protein> is a <protein> T-cell-specific transcription factor </protein> ."
  },
  {
    "input_text": "Curiously , the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter .",
    "target_text": "Curiously , the <protein> TCF-1 alpha </protein> binding element was inactive in vivo when removed from its neighboring elements on the <DNA> <protein> TCR </protein> alpha enhancer </DNA> and positioned in one or more copies upstream of a <DNA> heterologous promoter </DNA> ."
  },
  {
    "input_text": "Thus , the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 ( CREB ) transcription factors and the context of its binding site within the TCR alpha enhancer .",
    "target_text": "Thus , the transcriptional activity of <protein> TCF-1 alpha </protein> appears to depend on the <protein> TCF-2 alpha </protein> and <protein> T alpha 1 </protein> ( <protein> CREB </protein> ) <protein> transcription factors </protein> and the context of its binding site within the <DNA> <protein> TCR </protein> alpha enhancer </DNA> ."
  },
  {
    "input_text": "Tandem AP-1-binding sites within the human beta-globin dominant control region function as an inducible enhancer in erythroid cells .",
    "target_text": "<DNA> Tandem AP-1-binding sites </DNA> within the <DNA> human beta-globin dominant control region </DNA> function as an <DNA> inducible enhancer </DNA> in <cell_type> erythroid cells </cell_type> ."
  },
  {
    "input_text": "A powerful enhancer has been mapped to an 18-bp DNA segment located 11 kb 5' to the human epsilon-globin gene within the dominant control or locus-activating region .",
    "target_text": "A powerful enhancer has been mapped to an <DNA> 18-bp DNA segment </DNA> located 11 kb 5' to the <DNA> human epsilon-globin gene </DNA> within the <DNA> dominant control </DNA> or <DNA> locus-activating region </DNA> ."
  },
  {
    "input_text": "This enhancer is inducible in K562 human erythroleukemia cells , increasing linked gamma-globin promoter /luciferase gene expression to 170-fold over an enhancerless construct .",
    "target_text": "This <DNA> enhancer </DNA> is inducible in <cell_line> K562 human erythroleukemia cells </cell_line> , increasing linked <DNA> gamma-globin promoter </DNA> <protein> /luciferase </protein> gene expression to 170-fold over an <DNA> enhancerless construct </DNA> ."
  },
  {
    "input_text": "The enhancer consists of tandem AP-1-binding sites , phased 10 bp apart , which are both required for full activity .",
    "target_text": "The <DNA> enhancer </DNA> consists of <DNA> tandem AP-1-binding sites </DNA> , phased 10 bp apart , which are both required for full activity ."
  },
  {
    "input_text": "DNA-protein binding assays with nuclear extracts from induced cells demonstrate a high molecular weight complex on the enhancer .",
    "target_text": "DNA-protein binding assays with nuclear extracts from induced cells demonstrate a <protein> high molecular weight complex </protein> on the <DNA> enhancer </DNA> ."
  },
  {
    "input_text": "The formation of this complex also requires both AP-1 sites and correlates with maximal enhancer activity .",
    "target_text": "The formation of this complex also requires both <DNA> AP-1 sites </DNA> and correlates with maximal <DNA> enhancer </DNA> activity ."
  },
  {
    "input_text": "Induction of the enhancer may have a role in the increase in globin gene transcription that characterizes erythroid maturation .",
    "target_text": "Induction of the <DNA> enhancer </DNA> may have a role in the increase in <DNA> globin gene </DNA> transcription that characterizes erythroid maturation ."
  },
  {
    "input_text": "Enhancer activity appears to be mediated by the binding of a complex of proteins from the jun and fos families to tandem AP-1 consensus sequences .",
    "target_text": "Enhancer activity appears to be mediated by the binding of a complex of proteins from the <DNA> jun and fos families </DNA> to <DNA> tandem AP-1 consensus sequences </DNA> ."
  },
  {
    "input_text": "Identification of a novel factor that interacts with an immunoglobulin heavy-chain promoter and stimulates transcription in conjunction with the lymphoid cell-specific factor OTF2 .",
    "target_text": "Identification of a <protein> novel factor </protein> that interacts with an <DNA> immunoglobulin heavy-chain promoter </DNA> and stimulates transcription in conjunction with the <protein> lymphoid cell-specific factor </protein> <protein> OTF2 </protein> ."
  },
  {
    "input_text": "The tissue-specific expression of the MOPC 141 immunoglobulin heavy-chain gene was studied by using in vitro transcription .",
    "target_text": "The tissue-specific expression of the <DNA> MOPC 141 immunoglobulin heavy-chain gene </DNA> was studied by using in vitro transcription ."
  },
  {
    "input_text": "B-cell-specific transcription of this gene was dependent on the octamer element 5'-ATGCAAAG-3' , located in the upstream region of this promoter and in the promoters of all other immunoglobulin heavy- and light- chain genes .",
    "target_text": "B-cell-specific transcription of this gene was dependent on the <DNA> octamer element </DNA> 5'-ATGCAAAG-3' , located in the <DNA> upstream region </DNA> of this <DNA> promoter </DNA> and in the <DNA> promoters </DNA> of all other immunoglobulin heavy- and light- chain genes ."
  },
  {
    "input_text": "The interaction of purified octamer transcription factors 1 and 2 ( OTF1 and OTF2 ) with the MOPC 141 promoter was studied by using electrophoretic mobility shift assays and DNase I footprinting .",
    "target_text": "The interaction of purified <protein> octamer <protein> transcription factors </protein> </protein> 1 and 2 ( <protein> OTF1 </protein> and <protein> OTF2 </protein> ) with the <DNA> MOPC 141 promoter </DNA> was studied by using electrophoretic mobility shift assays and <protein> DNase I </protein> footprinting ."
  },
  {
    "input_text": "Purified OTF1 from HeLa cells and OTF1 and OTF2 from B cells bound to identical sequences within the heavy-chain promoter .",
    "target_text": "Purified <protein> OTF1 </protein> from <cell_line> HeLa cells </cell_line> and <protein> OTF1 </protein> and <protein> OTF2 </protein> from <cell_type> B cells </cell_type> bound to identical sequences within the <DNA> heavy-chain promoter </DNA> ."
  },
  {
    "input_text": "The OTF interactions we observed extended over the heptamer element 5'-CTCAGGA-3' , and it seems likely that the binding of the purified factors involves cooperation between octamer and heptamer sites in this promoter .",
    "target_text": "The OTF interactions we observed extended over the <DNA> heptamer element </DNA> 5'-CTCAGGA-3' , and it seems likely that the binding of the <protein> purified factors </protein> involves cooperation between octamer and heptamer sites in this <DNA> promoter </DNA> ."
  },
  {
    "input_text": "In addition to these elements , we identified a second regulatory element , the N element with the sequence 5'-GGAACCTCCCCC-3' .",
    "target_text": "In addition to these elements , we identified a second <DNA> regulatory element </DNA> , the <DNA> N element </DNA> with the sequence 5'-GGAACCTCCCCC-3' ."
  },
  {
    "input_text": "The N element could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts , and , in conjunction with the octamer element , it can promote high levels of transcription in B-cell extracts .",
    "target_text": "The <DNA> N element </DNA> could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts , and , in conjunction with the <DNA> octamer element </DNA> , it can promote high levels of transcription in B-cell extracts ."
  },
  {
    "input_text": "The N element bound a transcription factor , NTF , that is ubiquitous in cell-type distribution , and NTF was distinct from any of the previously described proteins that bind to similar sequences .",
    "target_text": "The <DNA> N element </DNA> bound a <protein> transcription factor </protein> , <protein> NTF </protein> , that is ubiquitous in <protein> cell-type distribution </protein> , and <protein> NTF </protein> was distinct from any of the <protein> previously described proteins </protein> that bind to similar sequences ."
  },
  {
    "input_text": "Based on these results , we propose that NTF and OTF2 interactions ( both with their cognate DNA elements and possibly at the protein-protein level ) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression .",
    "target_text": "Based on these results , we propose that <protein> NTF </protein> and <protein> OTF2 </protein> interactions ( both with their <DNA> cognate DNA elements </DNA> and possibly at the protein-protein level ) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression ."
  },
  {
    "input_text": "NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene .",
    "target_text": "<protein> NF-kappa B </protein> as inducible <protein> transcriptional activator </protein> of the <DNA> granulocyte-macrophage colony-stimulating factor gene </DNA> ."
  },
  {
    "input_text": "The expression of the gene encoding the granulocyte- macrophage colony-stimulating factor ( GM-CSF ) is induced upon activation of T cells with phytohemagglutinin and active phorbolester and upon expression of tax1 , a transactivating protein of the human T-cell leukemia virus type I .",
    "target_text": "The expression of the gene encoding the <protein> granulocyte- <protein> macrophage colony-stimulating factor </protein> </protein> ( <protein> GM-CSF </protein> ) is induced upon activation of <cell_type> T cells </cell_type> with <protein> phytohemagglutinin </protein> and active phorbolester and upon expression of <protein> tax1 </protein> , a <protein> transactivating protein </protein> of the human T-cell leukemia virus type I ."
  },
  {
    "input_text": "The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes , depending on promoter elements that bind the inducible transcription factor NF-kappa B ( or an NF-kappa B -like factor ) .",
    "target_text": "The same agents induce transcription from the interleukin-2 receptor alpha-chain and interleukin-2 genes , depending on <DNA> promoter elements </DNA> that bind the <protein> inducible transcription factor </protein> <protein> NF-kappa B </protein> ( or an <protein> <protein> NF-kappa B </protein> -like factor </protein> ) ."
  },
  {
    "input_text": "We therefore tested the possibility that the GM-CSF gene is also regulated by a cognate motif for the NF-kappa B transcription factor .",
    "target_text": "We therefore tested the possibility that the <DNA> <protein> GM-CSF </protein> gene </DNA> is also regulated by a cognate motif for the <protein> <protein> NF-kappa B </protein> transcription factor </protein> ."
  },
  {
    "input_text": "A recent functional analysis by Miyatake et al. ( S. Miyatake , M. Seiki , M. Yoshida , and K. Arai , Mol. Cell. Biol. 8 : 5581-5587 , 1988 ) described a short promoter region in the GM-CSF gene that conferred strong inducibility by T-cell-activating signals and tax1 , but no NF-kappa B -binding motifs were identified .",
    "target_text": "A recent functional analysis by Miyatake et al. ( S. Miyatake , M. Seiki , M. Yoshida , and K. Arai , Mol. Cell. Biol. 8 : 5581-5587 , 1988 ) described a <DNA> short promoter region </DNA> in the <DNA> <protein> GM-CSF </protein> gene </DNA> that conferred strong inducibility by T-cell-activating signals and <protein> tax1 </protein> , but no <DNA> <protein> NF-kappa B </protein> -binding motifs </DNA> were identified ."
  },
  {
    "input_text": "Using electrophoretic mobility shift assays , we showed binding of purified human NF-kappa B and of the NF-kappa B activated in Jurkat T cells to an oligonucleotide comprising the GM-CSF promoter element responsible for mediating responsiveness to T-cell-activating signals and tax1 .",
    "target_text": "Using electrophoretic mobility shift assays , we showed binding of purified <protein> human <protein> NF-kappa B </protein> </protein> and of the <protein> NF-kappa B </protein> activated in <cell_line> Jurkat <cell_type> T cells </cell_type> </cell_line> to an oligonucleotide comprising the <DNA> <protein> GM-CSF </protein> promoter element </DNA> responsible for mediating responsiveness to T-cell-activating signals and <protein> tax1 </protein> ."
  },
  {
    "input_text": "As shown by a methylation interference analysis and oligonucleotide competition experiments , purified NF-kappa B binds at positions -82 to -91 ( GGGAACTACC ) of the GM-CSF promoter sequence with an affinity similar to that with which it binds to the biologically functional kappa B motif in the beta interferon promoter ( GGGAAATTCC ) .",
    "target_text": "As shown by a methylation interference analysis and oligonucleotide competition experiments , purified <protein> NF-kappa B </protein> binds at <DNA> positions -82 to -91 </DNA> ( GGGAACTACC ) of the <DNA> <protein> GM-CSF </protein> promoter </DNA> sequence with an affinity similar to that with which it binds to the <DNA> biologically functional kappa B motif </DNA> in the <DNA> beta interferon promoter </DNA> ( GGGAAATTCC ) ."
  },
  {
    "input_text": "Two kappa B-like motifs at positions -98 to -108 of the GM-CSF promoter were also recognized but with much lower affinities .",
    "target_text": "Two <DNA> kappa B-like motifs </DNA> at <DNA> positions -98 to -108 </DNA> of the <DNA> <protein> GM-CSF </protein> promoter </DNA> were also recognized but with much lower affinities ."
  },
  {
    "input_text": "Our data provide strong evidence that the expression of the GM-CSF gene following T-cell activation is controlled by binding of the NF-kappa B transcription factor to a high-affinity binding site in the GM-CSF promoter .",
    "target_text": "Our data provide strong evidence that the expression of the <DNA> <protein> GM-CSF </protein> gene </DNA> following T-cell activation is controlled by binding of the <protein> <protein> NF-kappa B </protein> transcription factor </protein> to a <DNA> high-affinity binding site </DNA> in the <DNA> <protein> GM-CSF </protein> promoter </DNA> ."
  },
  {
    "input_text": "Effects of mitogenic agents upon glucocorticoid action in human tonsillar T- lymphocytes .",
    "target_text": "Effects of mitogenic agents upon glucocorticoid action in <cell_type> human tonsillar T- <cell_type> lymphocytes </cell_type> </cell_type> ."
  },
  {
    "input_text": "The treatment of human tonsillar T- lymphocytes with 4-phorbol 12-myristate 13-acetate ( PMA ) , resulted in about two fold increase in glucocorticoid receptor ( GR ) number , without any significant change in the receptor affinity .",
    "target_text": "The treatment of <cell_type> human tonsillar T- <cell_type> lymphocytes </cell_type> </cell_type> with 4-phorbol 12-myristate 13-acetate ( PMA ) , resulted in about two fold increase in <protein> glucocorticoid receptor </protein> ( <protein> GR </protein> ) number , without any significant change in the receptor affinity ."
  },
  {
    "input_text": "This increase disappeared in the presence of cycloheximide .",
    "target_text": "This increase disappeared in the presence of cycloheximide ."
  },
  {
    "input_text": "Alone , PMA and calcium ionophore A23187 did not affect , but together stimulated , like phytohaemagglutinin ( PHA ) , leucine and , in particular , thymidine incorporation .",
    "target_text": "Alone , PMA and calcium ionophore A23187 did not affect , but together stimulated , like <protein> phytohaemagglutinin </protein> ( <protein> PHA </protein> ) , leucine and , in particular , thymidine incorporation ."
  },
  {
    "input_text": "PMA enhanced slightly the stimulatory effect of PHA .",
    "target_text": "PMA enhanced slightly the stimulatory effect of <protein> PHA </protein> ."
  },
  {
    "input_text": "Alone , these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation ; however , PMA -A23187 and PMA -PHA combinations appeared to antagonize the suppression by dexamethasone .",
    "target_text": "Alone , these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation ; however , PMA -A23187 and PMA <protein> -PHA </protein> combinations appeared to antagonize the suppression by dexamethasone ."
  },
  {
    "input_text": "To be or not to be a responder in T-cell responses : ubiquitous oligopeptides in all proteins .",
    "target_text": "To be or not to be a responder in T-cell responses : ubiquitous oligopeptides in all proteins ."
  },
  {
    "input_text": "Amino acid sequences of all proteins are essays written in the same language .",
    "target_text": "Amino acid sequences of all proteins are essays written in the same language ."
  },
  {
    "input_text": "Accordingly , the same set of words and phrases ( oligopeptides ) appear in totally unrelated proteins .",
    "target_text": "Accordingly , the same set of words and phrases ( oligopeptides ) appear in totally <protein> unrelated proteins </protein> ."
  },
  {
    "input_text": "The reason that only certain individuals of particular major histocompatibility complex ( MHC ) haplotypes can mount T-cell responses against a given antigen of pathogens is found in the fact that T-cell receptors are designed to recognize 18-20 residue-long peptide fragments sandwiched between two alpha-helices of class I or class II MHC molecules .",
    "target_text": "The reason that only certain individuals of particular <protein> major histocompatibility complex ( MHC ) haplotypes </protein> can mount T-cell responses against a given antigen of pathogens is found in the fact that <protein> T-cell receptors </protein> are designed to recognize 18-20 residue-long peptide fragments sandwiched between two <protein> alpha-helices </protein> of <protein> class I </protein> or <protein> class II MHC molecules </protein> ."
  },
  {
    "input_text": "At this range of peptide lengths , most would appear as self , while nonselfness of the remainders are destined to be quite ambiguous , hence creating responders and nonresponders .",
    "target_text": "At this range of peptide lengths , most would appear as self , while nonselfness of the remainders are destined to be quite ambiguous , hence creating responders and nonresponders ."
  },
  {
    "input_text": "Two distinct signal transmission pathways in T lymphocytes are inhibited by complexes formed between an immunophilin and either FK506 or rapamycin .",
    "target_text": "Two distinct signal transmission pathways in <cell_type> T lymphocytes </cell_type> are inhibited by complexes formed between an <protein> immunophilin </protein> and either FK506 or rapamycin ."
  },
  {
    "input_text": "Proliferation and immunologic function of T lymphocytes are initiated by signals from the antigen receptor that are inhibited by the immunosuppressant FK506 but not by its structural analog , rapamycin .",
    "target_text": "Proliferation and immunologic function of <cell_type> T lymphocytes </cell_type> are initiated by signals from the <protein> antigen receptor </protein> that are inhibited by the immunosuppressant FK506 but not by its structural analog , rapamycin ."
  },
  {
    "input_text": "On the other hand , interleukin 2 ( IL-2 ) -induced signals are blocked by rapamycin but not by FK506 .",
    "target_text": "On the other hand , <protein> interleukin 2 </protein> ( <protein> IL-2 </protein> ) -induced signals are blocked by rapamycin but not by FK506 ."
  },
  {
    "input_text": "Remarkably , these two drugs inhibit each other 's actions , raising the possibility that both act by means of a common immunophilin ( immunosuppressant binding protein ) .",
    "target_text": "Remarkably , these two drugs inhibit each other 's actions , raising the possibility that both act by means of a common <protein> immunophilin </protein> ( <protein> immunosuppressant binding protein </protein> ) ."
  },
  {
    "input_text": "We find that the dissociation constant of rapamycin to the FK506 binding protein FKBP ( Kd = 0.2 nM ) is close to the dissociation constant of FK506 to FKBP ( Kd = 0.4 nM ) and to their effective biologic inhibitory concentrations .",
    "target_text": "We find that the dissociation constant of rapamycin to the <protein> FK506 binding protein </protein> <protein> FKBP </protein> ( Kd = 0.2 nM ) is close to the dissociation constant of FK506 to <protein> FKBP </protein> ( Kd = 0.4 nM ) and to their effective biologic inhibitory concentrations ."
  },
  {
    "input_text": "However , an excess of rapamycin is needed to revert FK506 -mediated inhibition of IL-2 production , apoptosis , and transcriptional activation of NF-AT , a T-cell-specific transcription factor necessary for IL-2 gene activation .",
    "target_text": "However , an excess of rapamycin is needed to revert FK506 -mediated inhibition of <protein> IL-2 </protein> production , apoptosis , and transcriptional activation of <protein> NF-AT </protein> , a <protein> T-cell-specific transcription factor </protein> necessary for <DNA> <protein> IL-2 </protein> gene </DNA> activation ."
  },
  {
    "input_text": "Similarly , an excess of FK506 is needed to revert rapamycin -mediated inhibition of IL-2 -induced proliferation .",
    "target_text": "Similarly , an excess of FK506 is needed to revert rapamycin -mediated inhibition of <protein> IL-2 </protein> -induced proliferation ."
  },
  {
    "input_text": "The drug concentrations required for antagonism may be explained by the relative affinity of the drugs to , and by the abundance of , the immunophilin FKBP .",
    "target_text": "The drug concentrations required for antagonism may be explained by the relative affinity of the drugs to , and by the abundance of , the <protein> immunophilin </protein> <protein> FKBP </protein> ."
  },
  {
    "input_text": "FKBP has been shown to catalyze the interconversion of the cis- and trans- rotamers of the peptidyl-prolyl amide bond of peptide substrates ; here we show that rapamycin , like FK506 , is a potent inhibitor of the rotamase activity of FKBP ( Ki = 0.2 nM ) .",
    "target_text": "<protein> FKBP </protein> has been shown to catalyze the interconversion of the cis- and trans- rotamers of the <protein> peptidyl-prolyl amide bond </protein> of peptide substrates ; here we show that rapamycin , like FK506 , is a potent inhibitor of the rotamase activity of <protein> FKBP </protein> ( Ki = 0.2 nM ) ."
  },
  {
    "input_text": "Neither FKBP binding nor inhibition of rotamase activity of FKBP alone is sufficient to explain the biologic actions of these drugs .",
    "target_text": "Neither <protein> FKBP </protein> binding nor inhibition of rotamase activity of <protein> FKBP </protein> alone is sufficient to explain the biologic actions of these drugs ."
  },
  {
    "input_text": "Rather , these findings suggest that immunophilin bound to FK506 interferes with antigen receptor -induced signals , while rapamycin bound to the immunophilin interferes with IL-2 -induced signals .",
    "target_text": "Rather , these findings suggest that <protein> immunophilin </protein> bound to FK506 interferes with <protein> antigen receptor </protein> -induced signals , while rapamycin bound to the <protein> immunophilin </protein> interferes with <protein> IL-2 </protein> -induced signals ."
  },
  {
    "input_text": "Adherence-dependent increase in human monocyte PDGF(B) mRNA is associated with increases in c-fos , c-jun , and EGR2 mRNA .",
    "target_text": "Adherence-dependent increase in <RNA> human monocyte PDGF(B) mRNA </RNA> is associated with increases in c-fos , c-jun , and EGR2 mRNA ."
  },
  {
    "input_text": "Adherence is an important initial step in the transition of a circulating monocyte to a tissue macrophage .",
    "target_text": "Adherence is an important initial step in the transition of a <cell_type> circulating monocyte </cell_type> to a <cell_type> tissue macrophage </cell_type> ."
  },
  {
    "input_text": "This differentiation is accompanied by an augmented capacity to generate growth factors .",
    "target_text": "This differentiation is accompanied by an augmented capacity to generate <protein> growth factors </protein> ."
  },
  {
    "input_text": "We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased mRNA encoding profibrotic growth factors such as platelet-derived growth factor B subunit ( PDGF[B] ) and transforming growth factor-beta ( TGF-beta ) .",
    "target_text": "We hypothesized that adherence itself might be an important trigger for a sequence of gene activation culminating in cells with increased <RNA> mRNA </RNA> encoding profibrotic <protein> growth factors </protein> such as <protein> platelet-derived growth factor B subunit </protein> ( <protein> PDGF[B] </protein> ) and <protein> transforming growth factor-beta </protein> ( <protein> TGF-beta </protein> ) ."
  },
  {
    "input_text": "After in vitro adherence , human monocytes had a biphasic increase in PDGF(B) mRNA with peaks at 6 h and 13 d .",
    "target_text": "After in vitro adherence , human monocytes had a biphasic increase in <RNA> <protein> PDGF(B) </protein> mRNA </RNA> with peaks at 6 h and 13 d ."
  },
  {
    "input_text": "No increase in TGF-beta mRNA was observed .",
    "target_text": "No increase in <RNA> <protein> TGF-beta </protein> mRNA </RNA> was observed ."
  },
  {
    "input_text": "The 6-h increase in PDGF(B) mRNA was adherence dependent , and in addition , was abrogated when the cytoskeletal integrity was compromised by cytochalasin D .",
    "target_text": "The 6-h increase in <RNA> <protein> PDGF(B) </protein> mRNA </RNA> was adherence dependent , and in addition , was abrogated when the cytoskeletal integrity was compromised by cytochalasin D ."
  },
  {
    "input_text": "The 6-h increase in PDGF(B) mRNA was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide .",
    "target_text": "The 6-h increase in <RNA> <protein> PDGF(B) </protein> mRNA </RNA> was unaltered by adherence in the presence of the monocyte stimulus lipopolysaccharide ."
  },
  {
    "input_text": "Adherence to either fibronectin or collagen-coated plastic had little consistent effect on PDGF(B) mRNA accumulation .",
    "target_text": "Adherence to either fibronectin or collagen-coated plastic had little consistent effect on <RNA> <protein> PDGF(B) </protein> mRNA </RNA> accumulation ."
  },
  {
    "input_text": "The increased PDGF(B) mRNA observed in adherent monocytes was accompanied by increases in mRNAs of the early growth response genes c-fos ( maximal at 20 min ) , c-jun , and EGR2 ( maximal at 6-24 h ) .",
    "target_text": "The increased <RNA> <protein> PDGF(B) </protein> mRNA </RNA> observed in <cell_type> adherent monocytes </cell_type> was accompanied by increases in <RNA> mRNAs </RNA> of the <DNA> early growth response genes </DNA> <DNA> c-fos </DNA> ( maximal at 20 min ) , c-jun , and EGR2 ( maximal at 6-24 h ) ."
  },
  {
    "input_text": "The increase in c-jun and EGR2 , but not c-fos , mRNA was also abrogated by cytochalasin D .",
    "target_text": "The increase in c-jun and EGR2 , but not <DNA> c-fos </DNA> , mRNA was also abrogated by cytochalasin D ."
  },
  {
    "input_text": "These observations suggest that adherence results in increases of c-fos , c-jun , EGR2 , and PDGF(B) mRNA .",
    "target_text": "These observations suggest that adherence results in increases of c-fos , c-jun , EGR2 , and PDGF(B) mRNA ."
  },
  {
    "input_text": "In addition , the increases in c-jun , EGR2 , and PDGF(B) may depend on cytoskeletal rearrangement .",
    "target_text": "In addition , the increases in <DNA> c-jun </DNA> , <DNA> EGR2 </DNA> , and <protein> PDGF(B) </protein> may depend on cytoskeletal rearrangement ."
  },
  {
    "input_text": "Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished .",
    "target_text": "Modulation of these events at the time of adherence offers a mechanism by which differential priming of the cells may be accomplished ."
  },
  {
    "input_text": "Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor .",
    "target_text": "Single cell assay of a <protein> transcription factor </protein> reveals a threshold in transcription activated by signals emanating from the <protein> T-cell antigen receptor </protein> ."
  },
  {
    "input_text": "Stimulation of T lymphocytes through their antigen receptor leads to the appearance of several transcription factors , including NF-AT and NF-kappa B , which are involved in regulating genes required for immunologic activation .",
    "target_text": "Stimulation of <cell_type> T lymphocytes </cell_type> through their <protein> antigen receptor </protein> leads to the appearance of several <protein> transcription factors </protein> , including <protein> NF-AT </protein> and <protein> NF-kappa B </protein> , which are involved in regulating genes required for immunologic activation ."
  },
  {
    "input_text": "To investigate the activity of a single transcription factor in individual viable cells , we have applied an assay that uses the fluorescence-activated cell sorter to quantitate beta-galactosidase ( beta-gal ) .",
    "target_text": "To investigate the activity of a single <protein> transcription factor </protein> in <cell_type> individual viable cells </cell_type> , we have applied an assay that uses the fluorescence-activated cell sorter to quantitate <protein> beta-galactosidase </protein> ( <protein> beta-gal </protein> ) ."
  },
  {
    "input_text": "We have analyzed the distribution of NF-AT transcriptional activity among T cells undergoing activation by using a construct in which three tandem copies of the NF-AT -binding site directs transcription of the lacZ gene .",
    "target_text": "We have analyzed the distribution of <protein> NF-AT </protein> transcriptional activity among <cell_type> T cells </cell_type> undergoing activation by using a construct in which three tandem copies of the <DNA> <protein> NF-AT </protein> -binding site </DNA> directs transcription of the <DNA> lacZ gene </DNA> ."
  },
  {
    "input_text": "Unexpectedly , stimulation of cloned stably transfected Jurkat T cells leads to a bimodal pattern of beta-gal expression in which some cells express no beta-gal and others express high levels .",
    "target_text": "Unexpectedly , stimulation of <cell_line> cloned stably transfected Jurkat <cell_type> T cells </cell_type> </cell_line> leads to a bimodal pattern of beta-gal expression in which some cells express no <protein> beta-gal </protein> and others express high levels ."
  },
  {
    "input_text": "This expression pattern can not be accounted for by cell-cycle position or heritable variation .",
    "target_text": "This expression pattern can not be accounted for by cell-cycle position or heritable variation ."
  },
  {
    "input_text": "Further results , in which beta-gal activity is correlated with NF-AT -binding activity , indicate that the concentration of NF-AT must exceed a critical threshold before transcription initiates .",
    "target_text": "Further results , in which <protein> beta-gal </protein> activity is correlated with <protein> NF-AT </protein> -binding activity , indicate that the concentration of <protein> NF-AT </protein> must exceed a critical threshold before transcription initiates ."
  },
  {
    "input_text": "This threshold likely reflects the NF-AT concentration-dependent assembly of transcription complexes at the promoter .",
    "target_text": "This threshold likely reflects the <protein> NF-AT </protein> concentration-dependent assembly of <protein> transcription complexes </protein> at the <DNA> promoter </DNA> ."
  },
  {
    "input_text": "Similar constructs controlled by NF-kappa B or the entire interleukin-2 enhancer show bimodal expression patterns during induction , suggesting that thresholds set by the concentration of transcription factors may be a common property of inducible genes .",
    "target_text": "Similar constructs controlled by <protein> NF-kappa B </protein> or the entire <DNA> interleukin-2 enhancer </DNA> show bimodal expression patterns during induction , suggesting that thresholds set by the concentration of <protein> transcription factors </protein> may be a common property of <DNA> inducible genes </DNA> ."
  },
  {
    "input_text": "The Epstein-Barr virus ( EBV ) BMRF1 promoter for early antigen ( EA-D ) is regulated by the EBV transactivators , BRLF1 and BZLF1 , in a cell-specific manner .",
    "target_text": "The <DNA> Epstein-Barr virus ( EBV ) BMRF1 promoter </DNA> for <protein> early antigen </protein> ( <protein> EA-D </protein> ) is regulated by the <protein> EBV transactivators </protein> , <protein> BRLF1 </protein> and <protein> BZLF1 </protein> , in a cell-specific manner ."
  },
  {
    "input_text": "The Epstein-Barr virus early antigen diffuse component ( EA-D ) is essential for Epstein-Barr virus DNA polymerase activity , and its activity is suppressed during latent infection .",
    "target_text": "The <protein> Epstein-Barr virus <protein> early antigen </protein> diffuse component </protein> ( <protein> EA-D </protein> ) is essential for Epstein-Barr <DNA> virus DNA </DNA> polymerase activity , and its activity is suppressed during latent infection ."
  },
  {
    "input_text": "We investigated the regulation of the promoter ( BMRF1 ) for this early gene by studying its responsiveness in vitro to two immediate-early viral transactivators , BZLF1 ( Z ) and BRLF1 ( R ) , focusing on the differences in response in lymphoid cells and epithelial cells .",
    "target_text": "We investigated the regulation of the <DNA> promoter </DNA> ( <DNA> BMRF1 </DNA> ) for this early gene by studying its responsiveness in vitro to two <protein> immediate-early viral transactivators </protein> , <protein> BZLF1 </protein> ( <protein> Z </protein> ) and <protein> BRLF1 </protein> ( <protein> R </protein> ) , focusing on the differences in response in <cell_type> lymphoid cells </cell_type> and <cell_type> epithelial cells </cell_type> ."
  },
  {
    "input_text": "In lymphoid cells , Z or R alone produced only small increases in EA-D promoter activity , whereas both transactivators together produced a large stimulatory effect .",
    "target_text": "In <cell_type> lymphoid cells </cell_type> , <protein> Z </protein> or <protein> R </protein> alone produced only small increases in <DNA> <protein> EA-D </protein> promoter </DNA> activity , whereas both <protein> transactivators </protein> together produced a large stimulatory effect ."
  },
  {
    "input_text": "In epithelial cells , the Z transactivator alone produced maximal stimulation of the EA-D promoter ; the effect of R and Z together was no greater than that of Z alone .",
    "target_text": "In <cell_type> epithelial cells </cell_type> , the <protein> Z transactivator </protein> alone produced maximal stimulation of the <DNA> <protein> EA-D </protein> promoter </DNA> ; the effect of <protein> R </protein> and <protein> Z </protein> together was no greater than that of <protein> Z </protein> alone ."
  },
  {
    "input_text": "Deletional analysis and site-directed mutagenesis of the EA-D promoter demonstrated that in epithelial cells the potential AP-1 binding site plays an essential role in Z responsiveness , although sequences further upstream are also important .",
    "target_text": "Deletional analysis and site-directed mutagenesis of the <DNA> <protein> EA-D </protein> promoter </DNA> demonstrated that in <cell_type> epithelial cells </cell_type> the potential <DNA> AP-1 binding site </DNA> plays an essential role in <protein> Z </protein> responsiveness , although sequences further upstream are also important ."
  },
  {
    "input_text": "In lymphoid cells , only the upstream sequences are required for transactivation by the Z/R combination , and the AP-1 site is dispensable .",
    "target_text": "In <cell_type> lymphoid cells </cell_type> , only the <DNA> upstream sequences </DNA> are required for transactivation by the <protein> Z/R </protein> combination , and the <protein> AP-1 site </protein> is dispensable ."
  },
  {
    "input_text": "These data suggest that EA-D ( BMRF1 ) promoter regulation by Z and R is cell type specific and appears to involve different mechanisms in each cell type .",
    "target_text": "These data suggest that <DNA> <protein> EA-D </protein> ( <DNA> BMRF1 </DNA> ) promoter </DNA> regulation by <protein> Z </protein> and <protein> R </protein> is cell type specific and appears to involve different mechanisms in each cell type ."
  },
  {
    "input_text": "Complementary DNA encoding the human T-cell FK506 -binding protein , a peptidylprolyl cis-trans isomerase distinct from cyclophilin .",
    "target_text": "<DNA> Complementary DNA </DNA> encoding the <protein> human T-cell FK506 -binding protein </protein> , a <protein> peptidylprolyl cis-trans isomerase </protein> distinct from <protein> cyclophilin </protein> ."
  },
  {
    "input_text": "The recently discovered macrolide FK506 has been demonstrated to have potent immunosuppressive activity at concentrations 100-fold lower than cyclosporin A , a cyclic undecapeptide that is used to prevent rejection after transplantation of bone marrow and organs , such as kidney , heart , and liver .",
    "target_text": "The recently discovered macrolide FK506 has been demonstrated to have potent immunosuppressive activity at concentrations 100-fold lower than cyclosporin A , a cyclic undecapeptide that is used to prevent rejection after transplantation of bone marrow and organs , such as kidney , heart , and liver ."
  },
  {
    "input_text": "After the recent discovery that the cyclosporin A -binding protein cyclophilin is identical to peptidylprolyl cis-trans isomerase , a cellular binding protein for FK506 was found to be distinct from cyclophilin but to have the same enzymatic activity .",
    "target_text": "After the recent discovery that the <protein> cyclosporin A -binding protein </protein> <protein> cyclophilin </protein> is identical to <protein> peptidylprolyl cis-trans isomerase </protein> , a <protein> cellular binding protein </protein> for FK506 was found to be distinct from <protein> cyclophilin </protein> but to have the same enzymatic activity ."
  },
  {
    "input_text": "In this study , we isolated a cDNA coding for FK506 -binding protein ( FKBP ) from human peripheral blood T cells by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence , Glu-Asp-Gly-Lys-Lys-Phe-Asp , reported for bovine FKBP .",
    "target_text": "In this study , we isolated a <DNA> cDNA </DNA> coding for FK506 -binding protein ( <protein> FKBP </protein> ) from human peripheral blood <cell_type> T cells </cell_type> by using mixed 20-mer oligonucleotide probes synthesized on the basis of the sequence , Glu-Asp-Gly-Lys-Lys-Phe-Asp , reported for <protein> bovine <protein> FKBP </protein> </protein> ."
  },
  {
    "input_text": "The DNA isolated contained an open reading frame encoding 108 amino acid residues .",
    "target_text": "The DNA isolated contained an open reading frame encoding 108 amino acid residues ."
  },
  {
    "input_text": "The first 40 residues of the deduced amino acid sequence were identical to those of the reported amino-terminal sequence of bovine FKBP , indicating that the DNA sequence isolated represents the gene coding for FKBP .",
    "target_text": "The first 40 residues of the deduced <protein> amino acid sequence </protein> were identical to those of the reported amino-terminal sequence of bovine <protein> FKBP </protein> , indicating that the DNA sequence isolated represents the gene coding for <protein> FKBP </protein> ."
  },
  {
    "input_text": "Computer-assisted analysis of the deduced amino acid sequence indicates that FKBP exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins , including cyclophilin .",
    "target_text": "Computer-assisted analysis of the deduced amino acid sequence indicates that <protein> FKBP </protein> exhibits no internal homology and does not have significant sequence similarity to any other amino acid sequences of known proteins , including <protein> cyclophilin </protein> ."
  },
  {
    "input_text": "This result suggests that two catalytically similar proteins , cyclophilin and FKBP , evolved independently .",
    "target_text": "This result suggests that two catalytically similar proteins , <protein> cyclophilin </protein> and <protein> FKBP </protein> , evolved independently ."
  },
  {
    "input_text": "In Northern blot analysis , mRNA species of approximately 1.8 kilobases that hybridized with human FKBP cDNA were detected in poly(A)+ RNAs from brain , lung , liver , and placental cells and leukocytes .",
    "target_text": "In Northern blot analysis , <RNA> mRNA species </RNA> of approximately 1.8 kilobases that hybridized with <DNA> human <protein> FKBP </protein> cDNA </DNA> were detected in <RNA> poly(A)+ RNAs </RNA> from brain , lung , liver , and <cell_type> placental cells </cell_type> and <cell_type> leukocytes </cell_type> ."
  },
  {
    "input_text": "Induction of Jurkat leukemic T cells with phorbol 12-myristate 13-acetate and ionomycin did not affect the level of FKBP mRNA .",
    "target_text": "Induction of <cell_line> Jurkat leukemic <cell_type> T cells </cell_type> </cell_line> with phorbol 12-myristate 13-acetate and ionomycin did not affect the level of <RNA> <protein> FKBP </protein> mRNA </RNA> ."
  },
  {
    "input_text": "Southern blot analysis of human genomic DNA digested with different restriction enzymes suggests the existence of only a few copies of the DNA sequence encoding FKBP .",
    "target_text": "Southern blot analysis of <DNA> human genomic DNA </DNA> digested with different <protein> restriction enzymes </protein> suggests the existence of only a few copies of the DNA sequence encoding <protein> FKBP </protein> ."
  },
  {
    "input_text": "This is in contrast to the result that as many as 20 copies of the cyclophilin gene and possible pseudogenes may be present in the mammalian genome .",
    "target_text": "This is in contrast to the result that as many as 20 copies of the <DNA> <protein> cyclophilin </protein> gene </DNA> and possible pseudogenes may be present in the <DNA> mammalian genome </DNA> ."
  },
  {
    "input_text": "Involvement of a second lymphoid-specific enhancer element in the regulation of immunoglobulin heavy-chain gene expression .",
    "target_text": "Involvement of a second <DNA> lymphoid-specific enhancer element </DNA> in the regulation of <DNA> immunoglobulin heavy-chain gene </DNA> expression ."
  },
  {
    "input_text": "To determine whether enhancer elements in addition to the highly conserved octamer ( OCTA ) -nucleotide motif are important for lymphoid-specific expression of the immunoglobulin heavy-chain ( IgH ) gene , we have investigated the effect of mutating the binding site for a putative additional lymphoid-specific transcription factor , designated NF-microB , in the murine IgH enhancer .",
    "target_text": "To determine whether <DNA> enhancer elements </DNA> in addition to the highly conserved <DNA> octamer ( OCTA ) -nucleotide motif </DNA> are important for lymphoid-specific expression of the <DNA> immunoglobulin heavy-chain ( IgH ) gene </DNA> , we have investigated the effect of mutating the <DNA> binding site </DNA> for a <protein> putative additional lymphoid-specific transcription factor </protein> , designated <protein> NF-microB </protein> , in the <DNA> murine IgH enhancer </DNA> ."
  },
  {
    "input_text": "We demonstrate that the NF-microB-binding site plays a critical role in the IgH enhancer , because mutation of the microB DNA motif decreased transcriptional activity of the IgH enhancer in cells of the B-cell lineage but not in nonlymphoid cells .",
    "target_text": "We demonstrate that the <DNA> NF-microB-binding site </DNA> plays a critical role in the <DNA> IgH enhancer </DNA> , because mutation of the microB DNA motif decreased transcriptional activity of the <DNA> IgH enhancer </DNA> in cells of the <cell_type> B-cell lineage </cell_type> but not in <cell_type> nonlymphoid cells </cell_type> ."
  },
  {
    "input_text": "This effect was comparable to or even stronger than the effect of a mutation in the OCTA site .",
    "target_text": "This effect was comparable to or even stronger than the effect of a mutation in the <DNA> OCTA site </DNA> ."
  },
  {
    "input_text": "Moreover , combined mutation of both microB and OCTA sites further reduced enhancer activity in lymphoid cells .",
    "target_text": "Moreover , combined mutation of both <DNA> microB </DNA> and <DNA> OCTA sites </DNA> further reduced enhancer activity in <cell_type> lymphoid cells </cell_type> ."
  },
  {
    "input_text": "Interestingly , alteration of either the microB or E3 site in a 70-base-pair fragment of the IgH enhancer that lacks the binding site for OCTA abolished enhancer activity in lymphoid cells completely .",
    "target_text": "Interestingly , alteration of either the <DNA> microB </DNA> or <DNA> E3 site </DNA> in a <DNA> 70-base-pair fragment </DNA> of the <DNA> IgH enhancer </DNA> that lacks the binding site for OCTA abolished enhancer activity in <cell_type> lymphoid cells </cell_type> completely ."
  },
  {
    "input_text": "Nevertheless , a multimer of the microB motif alone showed no enhancer activity .",
    "target_text": "Nevertheless , a multimer of the <DNA> <DNA> microB </DNA> motif </DNA> alone showed no enhancer activity ."
  },
  {
    "input_text": "DNase footprinting analysis corroborated the functional data showing that a lymphoid-specific protein binds to the microB DNA motif .",
    "target_text": "DNase footprinting analysis corroborated the functional data showing that a <protein> lymphoid-specific protein </protein> binds to the <DNA> <DNA> microB </DNA> DNA motif </DNA> ."
  },
  {
    "input_text": "Our results suggest that the microB element is a new crucial element important for lymphoid-specific expression of the IgH gene but that interaction with another enhancer element is essential for its activity .",
    "target_text": "Our results suggest that the <DNA> <DNA> microB </DNA> element </DNA> is a new crucial element important for lymphoid-specific expression of the IgH gene but that interaction with another <DNA> enhancer element </DNA> is essential for its activity ."
  },
  {
    "input_text": "Stimulation of the human immunodeficiency virus type 2 ( HIV-2 ) gene expression by the cytomegalovirus and HIV-2 transactivator gene .",
    "target_text": "Stimulation of the human immunodeficiency virus type 2 ( HIV-2 ) gene expression by the cytomegalovirus and <DNA> HIV-2 transactivator gene </DNA> ."
  },
  {
    "input_text": "Human immunodeficiency virus ( HIV ) often causes latent infection .",
    "target_text": "Human immunodeficiency virus ( HIV ) often causes latent infection ."
  },
  {
    "input_text": "Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis .",
    "target_text": "Transactivation by some DNA viruses has been implicated in inducing HIV-1 replication and pathogenesis ."
  },
  {
    "input_text": "The transactivator ( IE-2 ) gene of the human cytomegalovirus ( CMV ) can enhance HIV-2 as well as HIV-1 gene expression in vitro .",
    "target_text": "The <DNA> transactivator ( IE-2 ) gene </DNA> of the human cytomegalovirus ( CMV ) can enhance HIV-2 as well as HIV-1 gene expression in vitro ."
  },
  {
    "input_text": "This inducer can act in concert with the HIV-2 tat gene and T-cell activation in enhancing gene expression in human CD4+ lymphocytes .",
    "target_text": "This inducer can act in concert with the <DNA> HIV-2 tat gene </DNA> and T-cell activation in enhancing gene expression in <cell_type> human CD4+ lymphocytes </cell_type> ."
  },
  {
    "input_text": "While the HIV-2 and HIV-1 tat genes and T-cell activators apparently employ independent modes of action , the CMV transactivator in combination with the HIV-2 tat or T-cell activators may employ a gene activation pathway with some common and some distinct components .",
    "target_text": "While the HIV-2 and <DNA> HIV-1 tat genes </DNA> and <protein> T-cell activators </protein> apparently employ independent modes of action , the <DNA> CMV transactivator </DNA> in combination with the <DNA> HIV-2 tat </DNA> or <protein> T-cell activators </protein> may employ a gene activation pathway with some common and some distinct components ."
  },
  {
    "input_text": "Both HIV-2 and CMV transactivators enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation , with CMV transactivator affecting elongation more than the initiation .",
    "target_text": "Both HIV-2 and <DNA> CMV <protein> transactivators </protein> </DNA> enhance HIV-2 gene expression by transcriptional activation involving transcript initiation as well as elongation , with <DNA> CMV <protein> transactivator </protein> </DNA> affecting elongation more than the initiation ."
  },
  {
    "input_text": "A significant proportion of transcripts appear to terminate prematurely in the absence of transactivators .",
    "target_text": "A significant proportion of <RNA> transcripts </RNA> appear to terminate prematurely in the absence of <protein> transactivators </protein> ."
  },
  {
    "input_text": "Deletion mutation analysis of the HIV-2 long terminal repeat ( LTR ) suggests that the element that responds to CMV transactivation in human CD4+ lymphocytes is either a diffuse one or located downstream of the HIV-2 enhancer element .",
    "target_text": "Deletion mutation analysis of the <DNA> HIV-2 long terminal repeat </DNA> ( <DNA> LTR </DNA> ) suggests that the element that responds to CMV transactivation in <cell_type> human CD4+ lymphocytes </cell_type> is either a diffuse one or located downstream of the <DNA> HIV-2 enhancer element </DNA> ."
  },
  {
    "input_text": "Quantitative immunohistochemical analysis of mononuclear infiltrates in breast carcinomas -- correlation with tumour differentiation .",
    "target_text": "Quantitative immunohistochemical analysis of <cell_type> mononuclear infiltrates </cell_type> in breast carcinomas -- correlation with tumour differentiation ."
  },
  {
    "input_text": "Inflammatory infiltrates were analysed in tissue sections of 76 breast carcinomas by counting the percentage of macrophages , IgA+ and IgG+ plasma cells , T cells with their subpopulations , and natural killer cells , and by measuring postcapillary venules ( PCVs , found in 12 cases ) within the infiltrates .",
    "target_text": "<cell_type> Inflammatory infiltrates </cell_type> were analysed in tissue sections of 76 breast carcinomas by counting the percentage of <cell_type> macrophages </cell_type> , IgA+ and IgG+ plasma cells , <cell_type> T cells </cell_type> with their subpopulations , and <cell_type> natural killer cells </cell_type> , and by measuring postcapillary venules ( PCVs , found in 12 cases ) within the infiltrates ."
  },
  {
    "input_text": "These parameters were correlated with nuclear grade and biochemically determined hormone receptor status , known markers of tumour differentiation .",
    "target_text": "These parameters were correlated with nuclear grade and biochemically determined hormone receptor status , known markers of tumour differentiation ."
  },
  {
    "input_text": "A direct correlation was found between the extent of inflammation and nuclear grade ( P less than 0.0001 ) , and an inverse correlation between inflammation and oestrogen receptor ( OR ) positivity ( P less than 0.05 ) as well as inflammation and progesterone receptor ( PR ) positivity ( P less than 0.05 ) .",
    "target_text": "A direct correlation was found between the extent of inflammation and nuclear grade ( P less than 0.0001 ) , and an inverse correlation between inflammation and <protein> oestrogen receptor </protein> ( <protein> OR </protein> ) positivity ( P less than 0.05 ) as well as inflammation and <protein> progesterone receptor </protein> ( <protein> PR </protein> ) positivity ( P less than 0.05 ) ."
  },
  {
    "input_text": "The percentage of the OKT8+ suppressor/cytotoxic T cells increased when the inflammation expanded from scanty to moderate ( P less than 0.02 ) .",
    "target_text": "The percentage of the <cell_line> OKT8+ suppressor/cytotoxic <cell_type> T cells </cell_type> </cell_line> increased when the inflammation expanded from scanty to moderate ( P less than 0.02 ) ."
  },
  {
    "input_text": "The diameter of the PCVs also increased with increasing inflammatory infiltrate ( P less than 0.02 ) .",
    "target_text": "The diameter of the PCVs also increased with increasing inflammatory infiltrate ( P less than 0.02 ) ."
  },
  {
    "input_text": "In addition , a direct correlation exists between the diameter of the PCVs and both the percentage of the OKT8+ T cells ( P less than 0.04 ) and the Leu-7+ natural killer cells ( P less than 0.03 ) .",
    "target_text": "In addition , a direct correlation exists between the diameter of the PCVs and both the percentage of the <cell_line> OKT8+ <cell_type> T cells </cell_type> </cell_line> ( P less than 0.04 ) and the Leu-7+ <cell_type> natural killer cells </cell_type> ( P less than 0.03 ) ."
  },
  {
    "input_text": "Reactivity of lymphocytes to a progesterone receptor-specific monoclonal antibody .",
    "target_text": "Reactivity of <cell_line> lymphocytes </cell_line> to a <protein> progesterone receptor-specific monoclonal antibody </protein> ."
  },
  {
    "input_text": "In this study we present evidence for reactivity of pregnancy lymphocytes , but not nonpregnancy lymphocytes , with the progesterone receptor-specific monoclonal antibody mPRI .",
    "target_text": "In this study we present evidence for reactivity of <cell_type> pregnancy <cell_line> lymphocytes </cell_line> </cell_type> , but not <cell_type> nonpregnancy <cell_line> lymphocytes </cell_line> </cell_type> , with the <protein> progesterone receptor-specific monoclonal antibody </protein> <protein> mPRI </protein> ."
  },
  {
    "input_text": "Using an avidin -biotin peroxidase detection system , we found a nuclear staining in 14.6 +/- 3.7 % ( mean +/- SEM , N = 27 ) of pregnancy lymphocytes , while only 0.47 +/- 0.33 % ( mean +/- SEM , N = 15 ) of nonpregnancy lymphocytes reacted with the antibody .",
    "target_text": "Using an <protein> avidin </protein> <protein> -biotin peroxidase </protein> detection system , we found a nuclear staining in 14.6 +/- 3.7 % ( mean +/- SEM , N = 27 ) of <cell_type> pregnancy <cell_line> lymphocytes </cell_line> </cell_type> , while only 0.47 +/- 0.33 % ( mean +/- SEM , N = 15 ) of <cell_type> nonpregnancy <cell_line> lymphocytes </cell_line> </cell_type> reacted with the antibody ."
  },
  {
    "input_text": "To characterize the receptor-bearing subset , CD8+ and CD4+ cells were depleted by complement-dependent lysis .",
    "target_text": "To characterize the receptor-bearing subset , CD8+ and CD4+ cells were depleted by complement-dependent lysis ."
  },
  {
    "input_text": "Depletion of CD8+ cells was accompanied by 62 +/- 18 % loss of progesterone receptor -bearing cells , while depletion of CD4+ cells resulted in a twofold increase in the number of positively staining lymphocytes .",
    "target_text": "Depletion of <cell_line> CD8+ cells </cell_line> was accompanied by 62 +/- 18 % loss of <cell_line> <protein> progesterone receptor </protein> -bearing cells </cell_line> , while depletion of <cell_line> CD4+ cells </cell_line> resulted in a twofold increase in the number of positively staining <cell_line> lymphocytes </cell_line> ."
  },
  {
    "input_text": "In nonpregnancy lymphocytes a 3-day PHA treatment , as well as allogeneic stimulation , resulted in a significant increase in the number of receptor-containing cells .",
    "target_text": "In <cell_line> nonpregnancy <cell_line> lymphocytes </cell_line> </cell_line> a 3-day <protein> PHA </protein> treatment , as well as allogeneic stimulation , resulted in a significant increase in the number of <cell_type> receptor-containing cells </cell_type> ."
  },
  {
    "input_text": "These results suggest that pregnancy , but not nonpregnancy , lymphocytes contain progesterone binding structures , and that these are inducible by mitogenic or alloantigenic stimuli .",
    "target_text": "These results suggest that pregnancy , but not nonpregnancy , <cell_line> lymphocytes </cell_line> contain <protein> progesterone binding structures </protein> , and that these are inducible by mitogenic or alloantigenic stimuli ."
  },
  {
    "input_text": "Activation of human CD4 T lymphocytes .",
    "target_text": "Activation of <cell_line> human CD4 T lymphocytes </cell_line> ."
  },
  {
    "input_text": "Interaction of fibronectin with VLA-5 receptor on CD4 cells induces the AP-1 transcription factor .",
    "target_text": "Interaction of <protein> fibronectin </protein> with <protein> VLA-5 receptor </protein> on <cell_line> CD4 cells </cell_line> induces the <protein> AP-1 transcription factor </protein> ."
  },
  {
    "input_text": "Fibronectin synergized with anti-CD3 antibody to promote CD4 cell proliferation in a serum-free culture system whereas no proliferation was observed when CD4 cells were cultured with anti-CD3 alone or fibronectin alone .",
    "target_text": "<protein> Fibronectin </protein> synergized with <protein> anti-CD3 antibody </protein> to promote <protein> CD4 </protein> cell proliferation in a serum-free culture system whereas no proliferation was observed when <cell_line> CD4 cells </cell_line> were cultured with <protein> anti-CD3 </protein> alone or <protein> fibronectin </protein> alone ."
  },
  {
    "input_text": "In addition , anti-CD29 ( integrin beta 1 ) as well as anti-VLA-5 ( human fibronectin receptor ) antibodies blocked this CD4 cell activation in this system .",
    "target_text": "In addition , <protein> anti-CD29 </protein> ( <protein> integrin beta 1 </protein> ) as well as <protein> anti-VLA-5 </protein> ( <protein> human <protein> fibronectin </protein> receptor </protein> ) antibodies blocked this <cell_line> CD4 cell </cell_line> activation in this system ."
  },
  {
    "input_text": "Although anti-CD3 alone or fibronectin alone can not induce IL-2 message by CD4 cells , the combination of anti-CD3 plus fibronectin induced IL-2 message by CD4 cells .",
    "target_text": "Although <protein> anti-CD3 </protein> alone or <protein> fibronectin </protein> alone can not induce <protein> IL-2 </protein> message by <cell_line> CD4 cells </cell_line> , the combination of <protein> anti-CD3 </protein> plus <protein> fibronectin </protein> induced <protein> IL-2 </protein> message by <cell_line> CD4 cells </cell_line> ."
  },
  {
    "input_text": "In an analysis of the molecular mechanism by which IL-2 message was generated , we showed that a fibronectin -VLA-5 fibronectin receptor interaction may contribute an independent signal distinct from the CD3 pathway of activation by the induction of an AP-1 transcriptional factor .",
    "target_text": "In an analysis of the molecular mechanism by which <protein> IL-2 </protein> message was generated , we showed that a <protein> fibronectin </protein> -VLA-5 <protein> <protein> fibronectin </protein> receptor </protein> interaction may contribute an independent signal distinct from the <protein> CD3 </protein> pathway of activation by the induction of an <protein> AP-1 transcriptional factor </protein> ."
  },
  {
    "input_text": "Thus the VLA-5 fibronectin receptor on CD4 cells can play a complementary role in CD3 - TCR -mediated signal transduction through its interaction with fibronectin .",
    "target_text": "Thus the <protein> VLA-5 <protein> fibronectin </protein> receptor </protein> on <cell_line> CD4 cells </cell_line> can play a complementary role in <protein> CD3 </protein> - <protein> TCR </protein> -mediated signal transduction through its interaction with <protein> fibronectin </protein> ."
  },
  {
    "input_text": "Glucocorticoid receptors on mononuclear leukocytes in Alzheimer 's disease .",
    "target_text": "<protein> Glucocorticoid receptors </protein> on <cell_type> mononuclear leukocytes </cell_type> in Alzheimer 's disease ."
  },
  {
    "input_text": "Several lines of evidence suggest disturbances of the hypothalamic-pituitary-adrenal ( HPA ) system in Alzheimer 's disease ( AD ) .",
    "target_text": "Several lines of evidence suggest disturbances of the hypothalamic-pituitary-adrenal ( HPA ) system in Alzheimer 's disease ( AD ) ."
  },
  {
    "input_text": "In an exploration of the potential role of the glucocorticoid receptor ( GR ) in AD , GR density and affinity were assessed on mononuclear leukocytes of 12 AD patients and 12 healthy controls .",
    "target_text": "In an exploration of the potential role of the glucocorticoid receptor ( GR ) in AD , GR density and affinity were assessed on <cell_type> mononuclear leukocytes </cell_type> of 12 AD patients and 12 healthy controls ."
  },
  {
    "input_text": "GR binding characteristics did not differ between patients and controls or between patients subdivided according to diagnosis or associated clinical features .",
    "target_text": "GR binding characteristics did not differ between patients and controls or between patients subdivided according to diagnosis or associated clinical features ."
  },
  {
    "input_text": "These data suggest that the abnormalities of the HPA system in AD are not related to a GR deficiency .",
    "target_text": "These data suggest that the abnormalities of the HPA system in AD are not related to a <protein> GR </protein> deficiency ."
  },
  {
    "input_text": "Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers : a role for hematopoietic growth factor release by tumor cells ?",
    "target_text": "Oncogene amplification correlates with dense lymphocyte infiltration in human breast cancers : a role for <protein> hematopoietic growth factor </protein> release by <cell_type> tumor cells </cell_type> ?"
  },
  {
    "input_text": "One hundred six primary breast cancer samples were analysed for c-erbB2 , int-2 , and c-myc gene amplification .",
    "target_text": "One hundred six primary breast cancer samples were analysed for c-erbB2 , int-2 , and c-myc gene amplification ."
  },
  {
    "input_text": "Surgically confirmed nodal involvement was observed in 42 % .",
    "target_text": "Surgically confirmed nodal involvement was observed in 42 % ."
  },
  {
    "input_text": "Level of gene amplification was studied by Southern and/or slot blot techniques .",
    "target_text": "Level of gene amplification was studied by Southern and/or slot blot techniques ."
  },
  {
    "input_text": "Amplified c-erbB2 gene sequences were present in 21.5 % of all samples .",
    "target_text": "Amplified <DNA> c-erbB2 gene sequences </DNA> were present in 21.5 % of all samples ."
  },
  {
    "input_text": "Int-2 was amplified in 13.1 % and c-myc was amplified in 10.3 % .",
    "target_text": "<DNA> Int-2 </DNA> was amplified in 13.1 % and <DNA> c-myc </DNA> was amplified in 10.3 % ."
  },
  {
    "input_text": "In a non-parametric test ( Kruskal-Wallis ) a strong negative association was found between high levels of c-erbB2 amplification and absence of estrogen receptor ( ER ) ( P = .0009 ) or progesterone receptor ( PR ) ( P = .011 ) expression .",
    "target_text": "In a non-parametric test ( Kruskal-Wallis ) a strong negative association was found between high levels of <DNA> c-erbB2 </DNA> amplification and absence of estrogen receptor ( ER ) ( P = .0009 ) or <protein> progesterone receptor </protein> ( <protein> PR </protein> ) ( P = .011 ) expression ."
  },
  {
    "input_text": "No correlations were found between all or high levels of amplification of each oncogene separately or combined with T , N , grade , multifocality of tumor , or associated carcinoma in situ .",
    "target_text": "No correlations were found between all or high levels of amplification of each oncogene separately or combined with T , N , grade , multifocality of tumor , or associated carcinoma in situ ."
  },
  {
    "input_text": "There was a trend approaching statistical significance for patients with c-erbB2 amplifications to have positive lymph nodes at surgery ( P = 0.09 ) .",
    "target_text": "There was a trend approaching statistical significance for patients with <DNA> c-erbB2 </DNA> amplifications to have positive lymph nodes at surgery ( P = 0.09 ) ."
  },
  {
    "input_text": "A somewhat surprising finding however was a very strong association between oncogene amplification and dense lymphocyte infiltration of the tumor ( P = .05 ) . This correlation is even stronger when only high levels of amplification are considered , either for each oncogene separately ( P = .0048 ) or in combination ( P = .0007 ) .",
    "target_text": "A somewhat surprising finding however was a very strong association between <DNA> oncogene </DNA> amplification and dense lymphocyte infiltration of the tumor ( P = .05 ) . This correlation is even stronger when only high levels of amplification are considered , either for each oncogene separately ( P = .0048 ) or in combination ( P = .0007 ) ."
  },
  {
    "input_text": "We propose that malignant cell cytokine production may help explain this observation .",
    "target_text": "We propose that malignant cell <protein> cytokine </protein> production may help explain this observation ."
  },
  {
    "input_text": "Suppression of signals required for activation of transcription factor NF-kappa B in cells constitutively expressing the HTLV-I Tax protein .",
    "target_text": "Suppression of signals required for activation of <protein> transcription factor <protein> NF-kappa B </protein> </protein> in cells constitutively expressing the <protein> HTLV-I Tax protein </protein> ."
  },
  {
    "input_text": "Transient short-term expression of the Tax protein of human T-cell leukemia virus type-I ( HTLV-I ) leads to activation of the pleiotropic transcription factor NF-kappa B .",
    "target_text": "Transient short-term expression of the <protein> Tax protein </protein> of human T-cell leukemia virus type-I ( HTLV-I ) leads to activation of the pleiotropic <protein> transcription factor <protein> NF-kappa B </protein> </protein> ."
  },
  {
    "input_text": "Consistent with findings obtained with transient expression assays , we observed marked accumulation of the transcription factor NF-kappa B in the nucleus of Namalwa B lymphoid cells , which constitutively express Tax .",
    "target_text": "Consistent with findings obtained with transient expression assays , we observed marked accumulation of the <protein> transcription factor <protein> NF-kappa B </protein> </protein> in the nucleus of <cell_line> Namalwa B lymphoid cells </cell_line> , which constitutively express <protein> Tax </protein> ."
  },
  {
    "input_text": "In contrast , NF-kappa B activity was not detected in the nucleus following long-term expression of Tax in Jurkat T lymphocytes .",
    "target_text": "In contrast , <protein> NF-kappa B </protein> activity was not detected in the nucleus following long-term expression of <protein> Tax </protein> in <cell_line> Jurkat T lymphocytes </cell_line> ."
  },
  {
    "input_text": "The ability of both mitogens and cytokines to activate NF-kappa B was also blocked in Jurkat cells constitutively expressing Tax .",
    "target_text": "The ability of both mitogens and <protein> cytokines </protein> to activate <protein> NF-kappa B </protein> was also blocked in <cell_line> Jurkat cells </cell_line> constitutively expressing <protein> Tax </protein> ."
  },
  {
    "input_text": "However , the activation of other mitogen-inducible transcription factors , such as Fos and Jun , was unaffected .",
    "target_text": "However , the activation of other <protein> mitogen-inducible transcription factors </protein> , such as <protein> Fos </protein> and <protein> Jun </protein> , was unaffected ."
  },
  {
    "input_text": "Thus , depending on the cellular environment , the short- and long-term effects of Tax expression can be quite different .",
    "target_text": "Thus , depending on the cellular environment , the short- and long-term effects of <protein> Tax </protein> expression can be quite different ."
  },
  {
    "input_text": "Consequently , one function of Tax in cells infected with HTLV-I might involve cell-type-specific suppression , as opposed to activation , of distinct signal pathways .",
    "target_text": "Consequently , one function of <protein> Tax </protein> in cells infected with HTLV-I might involve cell-type-specific suppression , as opposed to activation , of distinct signal pathways ."
  },
  {
    "input_text": "The cells lines described here should be useful for the delineation of signaling pathways utilized in the selective regulation of gene expression .",
    "target_text": "The cells lines described here should be useful for the delineation of signaling pathways utilized in the selective regulation of gene expression ."
  },
  {
    "input_text": "Interferon-gamma and the sexual dimorphism of autoimmunity .",
    "target_text": "<protein> Interferon-gamma </protein> and the sexual dimorphism of autoimmunity ."
  },
  {
    "input_text": "The sexual difference in the incidence of autoimmune diseases has remained an enigma for many years .",
    "target_text": "The sexual difference in the incidence of autoimmune diseases has remained an enigma for many years ."
  },
  {
    "input_text": "In the examination of the induction of autoimmunity in transgenic mice , evidence has been obtained further implicating the lymphokine interferon-gamma in the etiology of autoimmunity .",
    "target_text": "In the examination of the induction of autoimmunity in transgenic mice , evidence has been obtained further implicating the <protein> lymphokine </protein> <protein> interferon-gamma </protein> in the etiology of autoimmunity ."
  },
  {
    "input_text": "Sex steroid regulation of the production of this molecule , as well as other cytokines , may help explain the gender-specific differences in the immune system , including autoimmunity .",
    "target_text": "Sex steroid regulation of the production of this molecule , as well as other <protein> cytokines </protein> , may help explain the gender-specific differences in the immune system , including autoimmunity ."
  },
  {
    "input_text": "Cloning of a transcriptionally active human TATA binding factor .",
    "target_text": "Cloning of a <protein> transcriptionally active <protein> human TATA binding factor </protein> </protein> ."
  },
  {
    "input_text": "Transcription factor IID ( TFIID ) binds to the TATA box promoter element and regulates the expression of most eukaryotic genes transcribed by RNA polymerase II .",
    "target_text": "<protein> Transcription factor IID </protein> ( <protein> TFIID </protein> ) binds to the <DNA> TATA box promoter element </DNA> and regulates the expression of most <DNA> eukaryotic genes </DNA> transcribed by <protein> RNA polymerase II </protein> ."
  },
  {
    "input_text": "Complementary DNA ( cDNA ) encoding a human TFIID protein has been cloned .",
    "target_text": "<DNA> Complementary DNA </DNA> ( <DNA> cDNA </DNA> ) encoding a <protein> human <protein> TFIID </protein> protein </protein> has been cloned ."
  },
  {
    "input_text": "The human TFIID polypeptide has 339 amino acids and a molecular size of 37,745 daltons .",
    "target_text": "The <protein> human <protein> TFIID </protein> polypeptide </protein> has 339 amino acids and a molecular size of 37,745 daltons ."
  },
  {
    "input_text": "The carboxyl-terminal 181 amino acids of the human TFIID protein shares 80 % identity with the TFIID protein from Saccharomyces cerevisiae .",
    "target_text": "The <protein> carboxyl-terminal 181 amino acids </protein> of the <protein> human <protein> TFIID </protein> protein </protein> shares 80 % identity with the <protein> TFIID </protein> protein from Saccharomyces cerevisiae ."
  },
  {
    "input_text": "The amino terminus contains an unusual repeat of 38 consecutive glutamine residues and an X-Thr-Pro repeat .",
    "target_text": "The <protein> amino terminus </protein> contains an unusual repeat of 38 consecutive glutamine residues and an <protein> X-Thr-Pro repeat </protein> ."
  },
  {
    "input_text": "Expression of DNA in reticulocyte lysates or in Escherichia coli yielded a protein that was competent for both DNA binding and transcription activation .",
    "target_text": "Expression of <DNA> DNA </DNA> in reticulocyte lysates or in Escherichia coli yielded a protein that was competent for both DNA binding and transcription activation ."
  },
  {
    "input_text": "A novel T-cell trans-activator that recognizes a phorbol ester-inducible element of the interleukin-2 promoter .",
    "target_text": "A novel <protein> T-cell trans-activator </protein> that recognizes a <DNA> phorbol ester-inducible element </DNA> of the <DNA> <protein> interleukin-2 </protein> promoter </DNA> ."
  },
  {
    "input_text": "The interleukin 2 ( IL-2 ) gene promoter is recognized by several cell-type-specific and ubiquitous transcriptional regulators that integrate information transmitted by various signaling systems leading to IL-2 production and T-cell activation .",
    "target_text": "The <DNA> <protein> interleukin 2 </protein> ( <protein> IL-2 </protein> ) gene promoter </DNA> is recognized by several cell-type-specific and ubiquitous transcriptional regulators that integrate information transmitted by various signaling systems leading to <protein> IL-2 </protein> production and <cell_type> T-cell </cell_type> activation ."
  },
  {
    "input_text": "Using a combination of transfection , protein-DNA binding , and in vitro transcription methods , we have discovered the novel T-cell-specific transcriptional activator TCF-1 ( for T-Cell Factor-1 ) , which recognizes a T-cell-specific response element ( TCE ) located within the IL-2 promoter .",
    "target_text": "Using a combination of transfection , protein-DNA binding , and in vitro transcription methods , we have discovered the <protein> novel T-cell-specific transcriptional activator </protein> <protein> TCF-1 </protein> ( for <protein> T-Cell Factor-1 </protein> ) , which recognizes a <DNA> T-cell-specific response element </DNA> ( <DNA> TCE </DNA> ) located within the <DNA> <protein> IL-2 </protein> promoter </DNA> ."
  },
  {
    "input_text": "Although the TCE is similar in sequence to a consensus NF kappa B site , several criteria indicate that TCF-1 is distinct from NF kappa B .",
    "target_text": "Although the <DNA> TCE </DNA> is similar in sequence to a <DNA> consensus <DNA> <protein> NF kappa B </protein> site </DNA> </DNA> , several criteria indicate that <protein> TCF-1 </protein> is distinct from <protein> NF kappa B </protein> ."
  },
  {
    "input_text": "However , like NF kappa B , TCF-1 activity is induced by phorbol esters and other T-cell activators .",
    "target_text": "However , like <protein> NF kappa B </protein> , <protein> TCF-1 </protein> activity is induced by phorbol esters and other T-cell activators ."
  },
  {
    "input_text": "Risk factors for breast recurrence in premenopausal and postmenopausal patients with ductal cancers treated by conservation therapy .",
    "target_text": "Risk factors for breast recurrence in premenopausal and postmenopausal patients with ductal cancers treated by conservation therapy ."
  },
  {
    "input_text": "Risk factors for local failure were evaluated for 496 clinical Stage I-II patients with infiltrating ductal carcinomas ( median follow-up , 71 months ) treated by conservative surgery and radiotherapy .",
    "target_text": "Risk factors for local failure were evaluated for 496 clinical Stage I-II patients with infiltrating ductal carcinomas ( median follow-up , 71 months ) treated by conservative surgery and radiotherapy ."
  },
  {
    "input_text": "Monofactorial analysis identified the following factors to be correlated with increased risk : moderate/marked mononuclear cell reaction ( MCR ) , high histologic grade ( G ) , extensive intraductal component ( EIC ) , tumor necrosis , macroscopic multiplicity , estrogen receptor negativity , anatomic tumor size , age younger than 40 years , and vascular invasion .",
    "target_text": "Monofactorial analysis identified the following factors to be correlated with increased risk : moderate/marked mononuclear cell reaction ( MCR ) , high histologic grade ( G ) , extensive intraductal component ( EIC ) , tumor necrosis , macroscopic multiplicity , <protein> estrogen receptor </protein> negativity , anatomic tumor size , age younger than 40 years , and vascular invasion ."
  },
  {
    "input_text": "Only MCR , G , and EIC proved significant in Cox multivariate analysis .",
    "target_text": "Only MCR , G , and EIC proved significant in Cox multivariate analysis ."
  },
  {
    "input_text": "These risk factors were highly age dependent , with EIC markedly more prevalent in women younger than 50 , MCR and G in women younger than 40 .",
    "target_text": "These risk factors were highly age dependent , with EIC markedly more prevalent in women younger than 50 , MCR and G in women younger than 40 ."
  },
  {
    "input_text": "Separate Cox analysis for premenopausal patients showed that MCR /EIC determined risk independent of resection margins : tumors with MCR had a 28 % , and with EIC a 22 % probability of recurring locally by 5 years .",
    "target_text": "Separate Cox analysis for premenopausal patients showed that MCR /EIC determined risk independent of resection margins : tumors with MCR had a 28 % , and with EIC a 22 % probability of recurring locally by 5 years ."
  },
  {
    "input_text": "Premenopausal patients with neither risk factor had a very low failure rate ( 2.6 % at 5 years ) , regardless of age .",
    "target_text": "Premenopausal patients with neither risk factor had a very low failure rate ( 2.6 % at 5 years ) , regardless of age ."
  },
  {
    "input_text": "For postmenopausal patients risk of breast recurrence was determined both by adequacy of resection margins and grade , with a high local failure rate for patients having G3 tumors with positive or indeterminate margins ( 31 % at 5 years ) .",
    "target_text": "For postmenopausal patients risk of breast recurrence was determined both by adequacy of resection margins and grade , with a high local failure rate for patients having G3 tumors with positive or indeterminate margins ( 31 % at 5 years ) ."
  },
  {
    "input_text": "The authors conclude that the microscopic examination is the only useful tool for assessing the risk of local failure , which is quite low for the majority of patients treated with breast conservation .",
    "target_text": "The authors conclude that the microscopic examination is the only useful tool for assessing the risk of local failure , which is quite low for the majority of patients treated with breast conservation ."
  },
  {
    "input_text": "High-risk patients can be recognized morphologically .",
    "target_text": "High-risk patients can be recognized morphologically ."
  },
  {
    "input_text": "The age dependence of morphologic risk factors appears to explain the high local failure rate seen in patients younger than 40 .",
    "target_text": "The age dependence of morphologic risk factors appears to explain the high local failure rate seen in patients younger than 40 ."
  },
  {
    "input_text": "Tax -independent binding of multiple cellular factors to Tax -response element DNA of HTLV-I .",
    "target_text": "<protein> Tax </protein> -independent binding of multiple <protein> cellular factors </protein> to <DNA> <protein> Tax </protein> -response element DNA </DNA> of HTLV-I ."
  },
  {
    "input_text": "The human T-cell leukemia virus type I ( HTLV-I ) promoter contains three copies of imperfect repeats of a 21-base pair sequence designated here as TRE ( Tax -response element ) that is responsive to the virally encoded transactivator protein Tax .",
    "target_text": "The <DNA> human T-cell leukemia virus type I ( HTLV-I ) promoter </DNA> contains three copies of imperfect repeats of a 21-base pair sequence designated here as <DNA> TRE </DNA> ( <DNA> <protein> Tax </protein> -response element </DNA> ) that is responsive to the <protein> virally encoded transactivator protein </protein> <protein> Tax </protein> ."
  },
  {
    "input_text": "We have identified and separated four nuclear proteins from C81-66-45 cells , an HTLV-I immortalized Tax -expressing human T-lymphocyte line ( Salahuddin et al. , 1983 ) , that interact with the TRE -DNA , none of which are identical with the Tax -protein .",
    "target_text": "We have identified and separated four <protein> nuclear proteins </protein> from C81-66-45 cells , an <cell_line> HTLV-I immortalized <protein> Tax </protein> -expressing human T-lymphocyte line </cell_line> ( Salahuddin et al. , 1983 ) , that interact with the <DNA> <DNA> TRE </DNA> -DNA </DNA> , none of which are identical with the <protein> <protein> Tax </protein> -protein </protein> ."
  },
  {
    "input_text": "The proteins identified have molecular weights of about 32 , 36 to 42 , 50 and 110 kD .",
    "target_text": "The proteins identified have molecular weights of about 32 , 36 to 42 , 50 and 110 kD ."
  },
  {
    "input_text": "Four different methods were used to identify the proteins .",
    "target_text": "Four different methods were used to identify the proteins ."
  },
  {
    "input_text": "First , from different cell lines three or all four of the nuclear proteins were specifically cross-linked by UV irradiation to the radioactively labeled TRE -DNA fragment .",
    "target_text": "First , from different cell lines three or all four of the <protein> nuclear proteins </protein> were specifically cross-linked by UV irradiation to the radioactively labeled <DNA> <DNA> TRE </DNA> -DNA fragment </DNA> ."
  },
  {
    "input_text": "Second , TRE -DNA binding proteins sedimented through a glycerol density gradient at rates corresponding to proteins of native molecular weights of 35 to 50 kD and 110 kD .",
    "target_text": "Second , <protein> <DNA> TRE </DNA> -DNA binding proteins </protein> sedimented through a glycerol density gradient at rates corresponding to proteins of native molecular weights of 35 to 50 kD and 110 kD ."
  },
  {
    "input_text": "Third , only the 50 kD protein was retained on a biotinylated DNA-streptavidin matrix when the DNA fragment contained the TRE -DNA .",
    "target_text": "Third , only the <protein> 50 kD protein </protein> was retained on a biotinylated DNA-streptavidin matrix when the DNA fragment contained the <DNA> <DNA> TRE </DNA> -DNA </DNA> ."
  },
  {
    "input_text": "Fourth , extensive purification by several cycles of TRE -DNA affinity chromatography resulted in the 32 , 36 to 42 and 110 kD proteins and to less extent the 50 kD factor .",
    "target_text": "Fourth , extensive purification by several cycles of <DNA> TRE </DNA> -DNA affinity chromatography resulted in the 32 , 36 to 42 and 110 kD proteins and to less extent the <protein> 50 kD factor </protein> ."
  },
  {
    "input_text": "Two abundant proteins of 75 and 80 kD were competed out by poly[d(I-C)] in all reactions .",
    "target_text": "Two abundant proteins of 75 and 80 kD were competed out by poly[d(I-C)] in all reactions ."
  },
  {
    "input_text": "The cAMP-response element CRE , TGACGTCA , present in the 21 base-pair sequence , appears to be essential for specific protein- TRE -DNA interactions because mutation of the two G 's destroys this complex .",
    "target_text": "The <DNA> cAMP-response element </DNA> <DNA> CRE </DNA> , TGACGTCA , present in the <DNA> 21 base-pair sequence </DNA> , appears to be essential for specific protein- <DNA> TRE </DNA> -DNA interactions because mutation of the two G 's destroys this complex ."
  },
  {
    "input_text": "This result suggests that the cAMP response element binding protein , CREB , is involved in the protein- TRE -DNA complex and in mediating the Tax response .",
    "target_text": "This result suggests that the <protein> cAMP response element binding protein </protein> , <protein> CREB </protein> , is involved in the <protein> protein- <DNA> TRE </DNA> -DNA complex </protein> and in mediating the <protein> Tax </protein> response ."
  },
  {
    "input_text": "Two distinct transcription factors that bind the immunoglobulin enhancer microE5/kappa 2 motif .",
    "target_text": "Two distinct <protein> transcription factors </protein> that bind the <DNA> immunoglobulin enhancer </DNA> <DNA> microE5/kappa 2 motif </DNA> ."
  },
  {
    "input_text": "Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of ubiquitous and developmentally regulated proteins .",
    "target_text": "Activity of the immunoglobulin heavy and kappa light chain gene enhancers depends on a complex interplay of <protein> <protein> ubiquitous </protein> and <protein> developmentally regulated proteins </protein> </protein> ."
  },
  {
    "input_text": "Two complementary DNAs were isolated that encode proteins , denoted ITF-1 and ITF-2 , that are expressed in a variety of cell types and bind the microE5/kappa 2 motif found in both heavy and kappa light chain enhancers .",
    "target_text": "Two <DNA> complementary DNAs </DNA> were isolated that encode proteins , denoted <protein> ITF-1 </protein> and <protein> ITF-2 </protein> , that are expressed in a variety of cell types and bind the <DNA> microE5/kappa 2 motif </DNA> found in both heavy and kappa light chain enhancers ."
  },
  {
    "input_text": "The complementary DNAs are the products of distinct genes , yet both ITF-1 and ITF-2 are structurally and functionally similar .",
    "target_text": "The <DNA> complementary DNAs </DNA> are the products of distinct genes , yet both <protein> ITF-1 </protein> and <protein> ITF-2 </protein> are structurally and functionally similar ."
  },
  {
    "input_text": "The two proteins interact with one another through their putative helix-loop-helix motifs and each possesses a distinct domain that dictates transcription activation .",
    "target_text": "The two proteins interact with one another through their putative <protein> helix-loop-helix motifs </protein> and each possesses a distinct domain that dictates transcription activation ."
  },
  {
    "input_text": "Elevated glucocorticoid receptor concentrations before and after glucocorticoid therapy in peripheral mononuclear leukocytes of patients with atopic dermatitis .",
    "target_text": "Elevated <protein> glucocorticoid receptor </protein> concentrations before and after glucocorticoid therapy in <cell_type> peripheral mononuclear leukocytes </cell_type> of patients with atopic dermatitis ."
  },
  {
    "input_text": "The number and affinity of glucocorticoid binding sites in peripheral mononuclear leukocytes of patients with atopic dermatitis ( AD ) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment .",
    "target_text": "The number and affinity of glucocorticoid binding sites in <cell_type> peripheral mononuclear leukocytes </cell_type> of patients with atopic dermatitis ( AD ) and healthy controls were determined under baseline conditions and after a defined oral glucocorticoid treatment ."
  },
  {
    "input_text": "Patients with AD ( n = 15 ) exhibited significantly more glucocorticoid receptors ( GR ) per cell than the control group ( n = 22 ) , while the GR affinity did not differ .",
    "target_text": "Patients with AD ( n = 15 ) exhibited significantly more <protein> glucocorticoid receptors </protein> ( <protein> GR </protein> ) per cell than the control group ( n = 22 ) , while the <protein> GR </protein> affinity did not differ ."
  },
  {
    "input_text": "Methylprednisolone treatment resulted in a significant reduction of the GR sites per cell in the steroid-treated control group ( n = 10 ) in contrast to the patients .",
    "target_text": "Methylprednisolone treatment resulted in a significant reduction of the <protein> GR </protein> sites per cell in the steroid-treated control group ( n = 10 ) in contrast to the patients ."
  },
  {
    "input_text": "The dissociation constant was not affected by methylprednisolone treatment in either group .",
    "target_text": "The dissociation constant was not affected by methylprednisolone treatment in either group ."
  },
  {
    "input_text": "In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity , the elevated GR concentrations in AD lend support to the hypothesis of a compensatory GR upregulation due to an insufficient action of endogenous cortisol or to altered cAMP -induced GR expression .",
    "target_text": "In view of the therapeutic efficiency of glucocorticoids in AD and findings of abnormal cAMP and cAMP-phosphodiesterase activity , the elevated <protein> GR </protein> concentrations in AD lend support to the hypothesis of a compensatory <protein> GR </protein> upregulation due to an insufficient action of endogenous cortisol or to altered cAMP -induced <protein> GR </protein> expression ."
  },
  {
    "input_text": "The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes .",
    "target_text": "The actions of cyclosporin A and FK506 suggest a novel step in the activation of <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "Cyclosporin A and FK506 are immunosuppressive compounds that have similar inhibitory effects on the expression of several lymphokines produced by T lymphocytes .",
    "target_text": "Cyclosporin A and FK506 are immunosuppressive compounds that have similar inhibitory effects on the expression of several <protein> lymphokines </protein> produced by <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "Despite their similar effects the drugs bind to two different cytosolic protein , cyclophilin and FKBP respectively , which raises the possibility that they have different modes of action .",
    "target_text": "Despite their similar effects the drugs bind to two different <protein> cytosolic protein </protein> , <protein> cyclophilin </protein> and <protein> FKBP </protein> respectively , which raises the possibility that they have different modes of action ."
  },
  {
    "input_text": "Using constructs in which mRNA production controlled by a specific transcription factor could be readily measured we found that both cyclosporin A and FK506 completely inhibited transcription activated by NF-AT , NFIL2 A , NFIL2 B and partially inhibited transcription activated by NF kappa B .",
    "target_text": "Using constructs in which <RNA> mRNA </RNA> production controlled by a specific <protein> transcription factor </protein> could be readily measured we found that both cyclosporin A and FK506 completely inhibited transcription activated by <protein> NF-AT </protein> , <protein> NFIL2 A </protein> , <protein> NFIL2 B </protein> and partially inhibited transcription activated by <protein> NF kappa B </protein> ."
  },
  {
    "input_text": "Cyclosporin A and FK506 inhibited only transcriptional activation that was dependent on Ca2+ mobilization .",
    "target_text": "Cyclosporin A and FK506 inhibited only transcriptional activation that was dependent on Ca2+ mobilization ."
  },
  {
    "input_text": "However , cyclosporin A and FK506 did not inhibit Ca2+ mobilization dependent expression of c-fos mRNA indicating that only a subset of signalling pathways regulated by Ca2+ is sensitive to these drugs .",
    "target_text": "However , cyclosporin A and FK506 did not inhibit Ca2+ mobilization dependent expression of <RNA> c-fos mRNA </RNA> indicating that only a subset of signalling pathways regulated by Ca2+ is sensitive to these drugs ."
  },
  {
    "input_text": "Furthermore , we did not observe any qualitative differences between the effect of cyclosporin A and FK506 on six different transcription factors which suggests that these drugs may interfere with the activity of a novel Ca2+ dependent step that regulates several transcription factors .",
    "target_text": "Furthermore , we did not observe any qualitative differences between the effect of cyclosporin A and FK506 on six different <protein> transcription factors </protein> which suggests that these drugs may interfere with the activity of a novel Ca2+ dependent step that regulates several <protein> transcription factors </protein> ."
  },
  {
    "input_text": "The internal methionine codons of human T-cell leukemia virus type II rex gene are not required for p24rex production or virus replication and transformation .",
    "target_text": "The internal methionine codons of <DNA> human T-cell leukemia virus type II rex gene </DNA> are not required for <protein> p24rex </protein> production or virus replication and transformation ."
  },
  {
    "input_text": "Human T-cell leukemia virus types I ( HTLV-I ) and II ( HTLV-II ) have two nonstructural trans-acting regulatory genes , tax and rex , located in the 3' region of the viral genome .",
    "target_text": "Human T-cell leukemia virus types I ( HTLV-I ) and II ( HTLV-II ) have two <DNA> nonstructural trans-acting regulatory genes </DNA> , <DNA> tax </DNA> and <DNA> rex </DNA> , located in the <DNA> 3' region </DNA> of the <DNA> viral genome </DNA> ."
  },
  {
    "input_text": "The tax gene product ( HTLV-I p40tax and HTLV-II p37tax ) is the transcriptional activator of the viral long terminal repeat .",
    "target_text": "The <protein> <DNA> tax </DNA> gene product </protein> ( <protein> HTLV-I <DNA> p40tax </DNA> </protein> and <protein> HTLV-II <DNA> p37tax </DNA> </protein> ) is the transcriptional activator of the <DNA> viral long terminal repeat </DNA> ."
  },
  {
    "input_text": "The rex gene encodes two protein products , p27rex /p21rex and p26rex /p24rex in HTLV-I and HTLV-II , respectively .",
    "target_text": "The <DNA> rex gene </DNA> encodes two protein products , <protein> <protein> p27rex </protein> <protein> /p21rex </protein> </protein> and <protein> <protein> p26rex </protein> <protein> /p24rex </protein> </protein> in HTLV-I and HTLV-II , respectively ."
  },
  {
    "input_text": "Rex acts posttranscriptionally to facilitate accumulation of full-length gag/pol and singly spliced env mRNA in the cytoplasm of HTLV-infected cells .",
    "target_text": "<protein> Rex </protein> acts posttranscriptionally to facilitate accumulation of full-length <protein> gag/pol </protein> and singly spliced <RNA> env mRNA </RNA> in the cytoplasm of <cell_type> HTLV-infected cells </cell_type> ."
  },
  {
    "input_text": "Previous studies showed that the first ATG of the rex gene is critical for Rex production and function .",
    "target_text": "Previous studies showed that the first ATG of the <DNA> <DNA> rex </DNA> gene </DNA> is critical for <protein> Rex </protein> production and function ."
  },
  {
    "input_text": "The importance of the internal ATGs to Rex function is not known .",
    "target_text": "The importance of the internal ATGs to <protein> Rex </protein> function is not known ."
  },
  {
    "input_text": "However , in vitro mutagenesis of the HTLV-I rex gene has provided indirect evidence which suggests that p21rex , and by analogy HTLV-II p24rex , results from initiation at an internal AUG of the tax /rex mRNA .",
    "target_text": "However , in vitro mutagenesis of the HTLV-I <DNA> <DNA> rex </DNA> gene </DNA> has provided indirect evidence which suggests that <protein> p21rex </protein> , and by analogy HTLV-II <protein> p24rex </protein> , results from initiation at an internal AUG of the <RNA> <DNA> tax </DNA> <DNA> /rex </DNA> mRNA </RNA> ."
  },
  {
    "input_text": "By using an infectious molecular clone of HTLV-II , we investigated the importance of the internal ATGs of the rex gene on Rex protein production and function .",
    "target_text": "By using an infectious molecular clone of HTLV-II , we investigated the importance of the internal ATGs of the <DNA> <DNA> rex </DNA> gene </DNA> on <protein> Rex </protein> protein production and function ."
  },
  {
    "input_text": "Our results indicate that p24rex of HTLV-II is not initiated at an internal AUG and that the internal methionine codons are not crucial to the function of the rex gene and , ultimately , the transforming properties of the virus .",
    "target_text": "Our results indicate that <protein> p24rex </protein> of HTLV-II is not initiated at an internal AUG and that the internal methionine codons are not crucial to the function of the <DNA> rex gene </DNA> and , ultimately , the transforming properties of the virus ."
  },
  {
    "input_text": "Astrocytes and glioblastoma cells express novel octamer-DNA binding proteins distinct from the ubiquitous Oct-1 and B cell type Oct-2 proteins .",
    "target_text": "<cell_type> Astrocytes </cell_type> and <cell_type> glioblastoma cells </cell_type> express novel <protein> octamer-DNA binding proteins </protein> distinct from the <protein> <protein> ubiquitous Oct-1 </protein> and <protein> B cell type Oct-2 proteins </protein> </protein> ."
  },
  {
    "input_text": "The ' octamer ' sequence , ATGCAAAT or its complement ATTTGCAT , is a key element for the transcriptional regulation of immunoglobulin genes in B-lymphocytes as well as a number of housekeeping genes in all cell types .",
    "target_text": "The <DNA> ' octamer ' sequence </DNA> , ATGCAAAT or its complement ATTTGCAT , is a key element for the transcriptional regulation of <DNA> immunoglobulin genes </DNA> in <cell_type> B-lymphocytes </cell_type> as well as a number of <DNA> housekeeping genes </DNA> in all cell types ."
  },
  {
    "input_text": "In lymphocytes , the octamer-binding protein Oct-2A and variants thereof are thought to contribute to the B-cell specific gene expression , while the ubiquitous protein Oct-1 seems to control general octamer site -dependent transcription .",
    "target_text": "In <cell_type> lymphocytes </cell_type> , the <protein> octamer-binding protein </protein> <protein> Oct-2A </protein> and variants thereof are thought to contribute to the <DNA> B-cell specific gene </DNA> expression , while the ubiquitous protein Oct-1 seems to control general <DNA> octamer site </DNA> -dependent transcription ."
  },
  {
    "input_text": "Various other genes , for example interleukin-1 and MHC class II genes , contain an octamer sequence in the promoter and are expressed in cells of both the immune and nervous systems .",
    "target_text": "Various other genes , for example interleukin-1 and MHC class II genes , contain an <DNA> octamer sequence </DNA> in the <DNA> promoter </DNA> and are expressed in cells of both the immune and nervous systems ."
  },
  {
    "input_text": "This prompted us to analyze the octamer-binding proteins in the latter cells .",
    "target_text": "This prompted us to analyze the <protein> octamer-binding proteins </protein> in the latter cells ."
  },
  {
    "input_text": "Using the electrophoretic mobility shift assay , at least six novel octamer binding proteins were detected in nuclear extracts of cultured mouse astrocytes .",
    "target_text": "Using the electrophoretic mobility shift assay , at least six novel <protein> octamer binding proteins </protein> were detected in nuclear extracts of <cell_type> cultured mouse astrocytes </cell_type> ."
  },
  {
    "input_text": "These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines .",
    "target_text": "These proteins are differentially expressed in human glioblastoma and neuroblastoma cell lines ."
  },
  {
    "input_text": "The nervous system-derived ( N-Oct ) proteins bound to the octamer DNA sequence in a manner which is indistinguishable from the Oct-1 and Oct-2A proteins .",
    "target_text": "The <protein> nervous system-derived ( N-Oct ) proteins </protein> bound to the <DNA> octamer DNA sequence </DNA> in a manner which is indistinguishable from the <protein> Oct-1 </protein> and <protein> Oct-2A proteins </protein> ."
  },
  {
    "input_text": "The relationship of the N-Oct proteins to Oct-1 and Oct-2A was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant Oct-1 and Oct-2A proteins .",
    "target_text": "The relationship of the <protein> N-Oct proteins </protein> to <protein> Oct-1 </protein> and <protein> Oct-2A </protein> was analyzed by proteolytic clipping bandshift assays and by their reactivity towards antisera raised against recombinant <protein> Oct-1 </protein> and <protein> Oct-2A </protein> proteins ."
  },
  {
    "input_text": "On the basis of these assays , all N-Oct-factors were found to be distinct from the ubiquitous Oct-1 and the lymphoid-specific Oct-2A proteins .",
    "target_text": "On the basis of these assays , all <protein> N-Oct-factors </protein> were found to be distinct from the <protein> ubiquitous <protein> Oct-1 </protein> </protein> and the <protein> lymphoid-specific <protein> Oct-2A </protein> </protein> proteins ."
  },
  {
    "input_text": "In melanoma cells that contain the N-Oct-3 factor , a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an Oct-2A expression vector .",
    "target_text": "In <cell_type> melanoma cells </cell_type> that contain the <protein> N-Oct-3 factor </protein> , a transfected lymphocyte-specific promoter was neither activated nor was it repressed upon contransfection with an <DNA> <protein> Oct-2A </protein> expression vector </DNA> ."
  },
  {
    "input_text": "We therefore speculate that N-Oct-3 and other N-Oct factors have a specific role in gene expression in cells of the nervous system .",
    "target_text": "We therefore speculate that <protein> N-Oct-3 </protein> and other <protein> N-Oct factors </protein> have a specific role in gene expression in cells of the nervous system ."
  },
  {
    "input_text": "Detection in non-erythroid cells of a factor with the binding characteristics of the erythroid cell transcription factor EF1 .",
    "target_text": "Detection in <cell_type> non-erythroid cells </cell_type> of a factor with the binding characteristics of the <protein> erythroid cell transcription factor </protein> <protein> EF1 </protein> ."
  },
  {
    "input_text": "The erythroid transcription factor erythroid factor-1 ( EF1 ) plays a critical role in the transcription of erythroid-specific genes .",
    "target_text": "The <protein> erythroid transcription factor </protein> <protein> erythroid factor-1 </protein> ( <protein> EF1 </protein> ) plays a critical role in the transcription of <DNA> erythroid-specific genes </DNA> ."
  },
  {
    "input_text": "Here we report the presence of a factor with the mobility and sequence-specific DNA-binding characteristics of EF1 at low abundance in a wide variety of non-erythroid cell types .",
    "target_text": "Here we report the presence of a factor with the mobility and sequence-specific DNA-binding characteristics of <protein> EF1 </protein> at low abundance in a wide variety of <cell_type> non-erythroid cell types </cell_type> ."
  },
  {
    "input_text": "This is the first report of an EF1 -like activity in non-erythroid cells and indicates that this factor may play a role in the regulation of genes expressed in such cells .",
    "target_text": "This is the first report of an <protein> EF1 </protein> -like activity in <cell_type> non-erythroid cells </cell_type> and indicates that this factor may play a role in the regulation of <DNA> genes </DNA> expressed in such cells ."
  },
  {
    "input_text": "Protein kinase inhibitor H-7 blocks accumulation of unspliced mRNA of human T-cell leukemia virus type I ( HTLV-I ) .",
    "target_text": "Protein kinase inhibitor H-7 blocks accumulation of <RNA> unspliced mRNA </RNA> of human T-cell leukemia virus type I ( HTLV-I ) ."
  },
  {
    "input_text": "Rex , the post-transcriptional regulator of human T-cell leukemia virus type I ( HTLV-I ) , is known to induce accumulation of the unspliced viral gag-pol mRNA .",
    "target_text": "<protein> Rex </protein> , the <protein> post-transcriptional regulator </protein> of human T-cell leukemia virus type I ( HTLV-I ) , is known to induce accumulation of the <RNA> unspliced viral gag-pol mRNA </RNA> ."
  },
  {
    "input_text": "Rex is a phosphoprotein found in the cell nucleolus , whose function may be regulated by its localization and phosphorylation .",
    "target_text": "<protein> Rex </protein> is a <protein> phosphoprotein </protein> found in the cell nucleolus , whose function may be regulated by its localization and phosphorylation ."
  },
  {
    "input_text": "We have examined the role of phosphorylation on Rex function by using a protein kinase inhibitor , H-7 [ 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine ] .",
    "target_text": "We have examined the role of phosphorylation on <protein> Rex </protein> function by using a protein kinase inhibitor , H-7 [ 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine ] ."
  },
  {
    "input_text": "Treatment of an HTLV-I infected human T-cell line with H-7 blocked specifically accumulation of the unspliced gag-pol mRNA , resulting in the decreased Gag protein synthesis that corresponds with the decreased in vivo phosphorylation of Rex .",
    "target_text": "Treatment of an <cell_line> HTLV-I infected human T-cell line </cell_line> with H-7 blocked specifically accumulation of the <RNA> unspliced gag-pol mRNA </RNA> , resulting in the decreased <protein> Gag protein </protein> synthesis that corresponds with the decreased in vivo phosphorylation of <protein> Rex </protein> ."
  },
  {
    "input_text": "In contrast , other viral and cellular products have not been influenced by the level of H-7 used .",
    "target_text": "In contrast , other viral and cellular products have not been influenced by the level of H-7 used ."
  },
  {
    "input_text": "Therefore , the phosphorylation of Rex is required for the viral RNA partition of HTLV-I .",
    "target_text": "Therefore , the phosphorylation of <protein> Rex </protein> is required for the viral RNA partition of HTLV-I ."
  },
  {
    "input_text": "Increased glucocorticoid responsiveness of CD4+ T-cell clonal lines grown in serum-free media .",
    "target_text": "Increased glucocorticoid responsiveness of <cell_line> CD4+ T-cell clonal lines </cell_line> grown in serum-free media ."
  },
  {
    "input_text": "CEM-C7 , a human leukemic CD4+ T-lymphocyte cell line and three of its subclones , CEM-4R4 , CEM-3R43 , and ICR-27 , previously cultured in a medium supplemented with 5 to 10 % fetal bovine serum , have been adapted to serum-free media .",
    "target_text": "<cell_line> CEM-C7 </cell_line> , a <cell_line> human leukemic CD4+ T-lymphocyte cell line </cell_line> and three of its subclones , <cell_line> CEM-4R4 </cell_line> , <cell_line> CEM-3R43 </cell_line> , and <cell_line> ICR-27 </cell_line> , previously cultured in a medium supplemented with 5 to 10 % fetal bovine serum , have been adapted to serum-free media ."
  },
  {
    "input_text": "The best medium of those tested was RPMI 1640 supplemented with 5 micrograms/ml each transferrin and insulin + 5 ng/ml sodium selenite +/- 0.1 % bovine serum albumin .",
    "target_text": "The best medium of those tested was RPMI 1640 supplemented with 5 micrograms/ml each <protein> transferrin </protein> and <protein> insulin </protein> + 5 ng/ml sodium selenite +/- 0.1 % <protein> bovine serum albumin </protein> ."
  },
  {
    "input_text": "While growing either with or without albumin , the several clonal lines of CEM cells displayed growth similar to serum-supplemented cultures .",
    "target_text": "While growing either with or without albumin , the several <cell_line> clonal lines </cell_line> of <cell_line> CEM </cell_line> cells displayed growth similar to serum-supplemented cultures ."
  },
  {
    "input_text": "Cell proliferation of CEM-C7 cells cultured in both serum-free media has been sustained for 3 mo.",
    "target_text": "Cell proliferation of <cell_line> CEM-C7 </cell_line> cells cultured in both serum-free media has been sustained for 3 mo."
  },
  {
    "input_text": "with culture doubling times of about 25 h for both serum-supplemented and serum-free cultures ( viability greater than or equal to 90 % ) .",
    "target_text": "with culture doubling times of about 25 h for both serum-supplemented and serum-free cultures ( viability greater than or equal to 90 % ) ."
  },
  {
    "input_text": "Cell morphology remained essentially the same in serum-free or serum containing media .",
    "target_text": "Cell morphology remained essentially the same in serum-free or serum containing media ."
  },
  {
    "input_text": "The expression of CD4 , a marker for T-derived lymphoid cells , was not significantly different in serum-free medium .",
    "target_text": "The expression of <protein> CD4 </protein> , a marker for <cell_type> T-derived lymphoid cells </cell_type> , was not significantly different in serum-free medium ."
  },
  {
    "input_text": "When grown in serum-free medium , CEM-C7 cells exhibited increased steroid responsiveness as evidenced by increased glucocorticoid receptor binding sites , increased induction of glutamine synthetase , and cell lysis at lower concentrations of steroid .",
    "target_text": "When grown in serum-free medium , <cell_line> CEM-C7 </cell_line> cells exhibited increased steroid responsiveness as evidenced by increased <protein> glucocorticoid receptor </protein> binding sites , increased induction of <protein> glutamine synthetase </protein> , and cell lysis at lower concentrations of steroid ."
  },
  {
    "input_text": "Receptor mutant subclones of CEM-C7 , which are proven to be completely unresponsive to micromolar concentrations of dexamethasone when grown in serum-supplemented medium , become partially sensitive to the hormone after growth in defined medium .",
    "target_text": "Receptor mutant subclones of <cell_line> CEM-C7 </cell_line> , which are proven to be completely unresponsive to micromolar concentrations of dexamethasone when grown in serum-supplemented medium , become partially sensitive to the hormone after growth in defined medium ."
  },
  {
    "input_text": "The increased sensitivity of CEM-C7 cells and its subclones to dexamethasone in serum-free medium returned to previous levels when these cells were recultured in serum-containing medium .",
    "target_text": "The increased sensitivity of <cell_line> <cell_line> CEM-C7 </cell_line> cells </cell_line> and its subclones to dexamethasone in serum-free medium returned to previous levels when these cells were recultured in serum-containing medium ."
  },
  {
    "input_text": "Our results suggest that substances in serum influence steroid effects on these cells and that the molecular details of glucocorticoid hormone action may be pursued more precisely in a clearly defined culture medium .",
    "target_text": "Our results suggest that substances in serum influence steroid effects on these cells and that the molecular details of glucocorticoid hormone action may be pursued more precisely in a clearly defined culture medium ."
  },
  {
    "input_text": "[ Glucocorticoid receptors on human peripheral mononuclear and polymorphonuclear leucocytes : changes in patients with yang-deficiency ]",
    "target_text": "[ <protein> Glucocorticoid receptors </protein> on human peripheral mononuclear and polymorphonuclear leucocytes : changes in patients with yang-deficiency ]"
  },
  {
    "input_text": "It was found that , in former works , the glucocorticoid receptors ( GCR ) on peripheral mixed leucocytes in patients with Yang-deficiency were decreased .",
    "target_text": "It was found that , in former works , the <protein> glucocorticoid receptors </protein> ( <protein> GCR </protein> ) on <cell_type> peripheral mixed leucocytes </cell_type> in patients with Yang-deficiency were decreased ."
  },
  {
    "input_text": "In this work , the mixed leucocytes were further separated into mononuclear ( MNL ) and polymorphonuclear ( PML ) leucocytes , and GCR were determined in each part of leucocytes .",
    "target_text": "In this work , the <cell_type> mixed leucocytes </cell_type> were further separated into mononuclear ( MNL ) and polymorphonuclear ( PML ) leucocytes , and <protein> GCR </protein> were determined in each part of <cell_type> leucocytes </cell_type> ."
  },
  {
    "input_text": "GCR on MNL and PML in 6 Yang deficient patients were 3473 +/- 413 and 4433 +/- 651 sites/cell respectively , statistically significant from the normal control group ( 4462 +/- 962 and 5622 +/- 782 sites/cell respectively , P less than 0.05 ) .",
    "target_text": "<protein> GCR </protein> on <cell_type> MNL </cell_type> and <cell_type> PML </cell_type> in 6 Yang deficient patients were 3473 +/- 413 and 4433 +/- 651 sites/cell respectively , statistically significant from the normal control group ( 4462 +/- 962 and 5622 +/- 782 sites/cell respectively , P less than 0.05 ) ."
  },
  {
    "input_text": "GCR on MNL , PML and mixed leucocytes in 5 patients were determined simultaneously , and all lowered from the control group .",
    "target_text": "<protein> GCR </protein> on <cell_type> MNL </cell_type> , <cell_type> PML </cell_type> and <cell_type> mixed leucocytes </cell_type> in 5 patients were determined simultaneously , and all lowered from the control group ."
  },
  {
    "input_text": "The results were 3369 +/- 370 , 4986 +/- 419 and 4524 +/- 852 sites/cell respectively , with the lowest GCR on MNL and highest on PML .",
    "target_text": "The results were 3369 +/- 370 , 4986 +/- 419 and 4524 +/- 852 sites/cell respectively , with the lowest <protein> GCR </protein> on <cell_type> MNL </cell_type> and highest on <cell_type> PML </cell_type> ."
  },
  {
    "input_text": "The ubiquitous octamer-binding protein ( s ) is sufficient for transcription of immunoglobulin genes .",
    "target_text": "The <protein> ubiquitous octamer-binding protein </protein> ( s ) is sufficient for transcription of <DNA> immunoglobulin genes </DNA> ."
  },
  {
    "input_text": "All immunoglobulin genes contain a conserved octanucleotide promoter element , ATGCAAAT , which has been shown to be required for their normal B-cell-specific transcription .",
    "target_text": "All <DNA> immunoglobulin genes </DNA> contain a conserved <DNA> octanucleotide promoter element </DNA> , ATGCAAAT , which has been shown to be required for their normal B-cell-specific transcription ."
  },
  {
    "input_text": "Proteins that bind this octamer have been purified , and cDNAs encoding octamer-binding proteins have been cloned .",
    "target_text": "Proteins that bind this octamer have been purified , and <DNA> cDNAs </DNA> encoding <protein> octamer-binding proteins </protein> have been cloned ."
  },
  {
    "input_text": "Some of these proteins ( referred to as OTF-2 ) are lymphoid specific , whereas at least one other , and possibly more ( referred to as OTF-1 ) , is found ubiquitously in all cell types .",
    "target_text": "Some of these proteins ( referred to as <protein> OTF-2 </protein> ) are lymphoid specific , whereas at least one other , and possibly more ( referred to as <protein> OTF-1 </protein> ) , is found ubiquitously in all cell types ."
  },
  {
    "input_text": "The exact role of these different proteins in directing the tissue-specific expression of immunoglobulin genes is unclear .",
    "target_text": "The exact role of these different proteins in directing the tissue-specific expression of <DNA> immunoglobulin genes </DNA> is unclear ."
  },
  {
    "input_text": "We have identified two human pre-B-cell lines that contain extremely low levels of OTF-2 yet still express high levels of steady-state immunoglobulin heavy-chain mRNA in vivo and efficiently transcribe an immunoglobulin gene in vitro .",
    "target_text": "We have identified two <cell_line> human pre-B-cell lines </cell_line> that contain extremely low levels of <protein> OTF-2 </protein> yet still express high levels of <RNA> steady-state <protein> immunoglobulin heavy-chain </protein> mRNA </RNA> in vivo and efficiently transcribe an <DNA> immunoglobulin gene </DNA> in vitro ."
  },
  {
    "input_text": "Addition of a highly enriched preparation of OTF-1 made from one of these pre-B cells or from HeLa cells specifically stimulated in vitro transcription of an immunoglobulin gene .",
    "target_text": "Addition of a highly enriched preparation of <protein> OTF-1 </protein> made from one of these <cell_line> pre-B cells </cell_line> or from <cell_line> HeLa cells </cell_line> specifically stimulated in vitro transcription of an <DNA> immunoglobulin gene </DNA> ."
  },
  {
    "input_text": "Furthermore , OFT-1 appeared to have approximately the same transactivation ability as OTF-2 when normalized for binding activity .",
    "target_text": "Furthermore , OFT-1 appeared to have approximately the same transactivation ability as <protein> OTF-2 </protein> when normalized for binding activity ."
  },
  {
    "input_text": "These results suggest that OTF-1 , without OTF-2 , is sufficient for transcription of immunoglobulin genes and that OTF-2 alone is not responsible for the B-cell-specific regulation of immunoglobulin gene expression .",
    "target_text": "These results suggest that <protein> OTF-1 </protein> , without <protein> OTF-2 </protein> , is sufficient for transcription of <DNA> immunoglobulin genes </DNA> and that <protein> OTF-2 </protein> alone is not responsible for the B-cell-specific regulation of <DNA> immunoglobulin gene </DNA> expression ."
  },
  {
    "input_text": "Effects of aldosterone on intralymphocytic sodium and potassium in patients with essential hypertension .",
    "target_text": "Effects of aldosterone on intralymphocytic sodium and potassium in patients with essential hypertension ."
  },
  {
    "input_text": "In vitro binding of aldosterone to mineralocorticoid receptors on human mononuclear leukocytes ( HML ) and its effects on the intracellular sodium and potassium concentrations of HML have already been described .",
    "target_text": "In vitro binding of aldosterone to <protein> mineralocorticoid receptors </protein> on <cell_type> human mononuclear leukocytes </cell_type> ( <cell_type> HML </cell_type> ) and its effects on the intracellular sodium and potassium concentrations of <cell_type> HML </cell_type> have already been described ."
  },
  {
    "input_text": "In the present paper this easily accessible human cell model was investigated in 13 patients with essential hypertension .",
    "target_text": "In the present paper this easily accessible human cell model was investigated in 13 patients with essential hypertension ."
  },
  {
    "input_text": "In only four patients sodium in HML without incubation was elevated compared with the range for normal persons .",
    "target_text": "In only four patients sodium in <cell_type> HML </cell_type> without incubation was elevated compared with the range for normal persons ."
  },
  {
    "input_text": "A decrease of intracellular sodium or potassium occurred during incubation without aldosterone ( P less than 0.02 ) .",
    "target_text": "A decrease of intracellular sodium or potassium occurred during incubation without aldosterone ( P less than 0.02 ) ."
  },
  {
    "input_text": "The addition of 1.4 nM aldosterone did not prevent this loss of electrolytes as observed in normal persons .",
    "target_text": "The addition of 1.4 nM aldosterone did not prevent this loss of electrolytes as observed in normal persons ."
  },
  {
    "input_text": "Plasma renin activity and aldosterone were not correlated with the electrolyte response and were within the normal limits .",
    "target_text": "<protein> Plasma renin </protein> activity and aldosterone were not correlated with the electrolyte response and were within the normal limits ."
  },
  {
    "input_text": "The number of mineralocorticoid receptors /cell were within or close to the normal range ( n = 9 ) .",
    "target_text": "The number of <protein> mineralocorticoid receptors </protein> /cell were within or close to the normal range ( n = 9 ) ."
  },
  {
    "input_text": "The independence of intracellular electrolytes from aldosterone despite a normal number of mineralocorticoid receptors may reflect an impairment of the mineralocorticoid effector mechanism in the HML of patients with essential hypertension .",
    "target_text": "The independence of intracellular electrolytes from aldosterone despite a normal number of <protein> mineralocorticoid receptors </protein> may reflect an impairment of the mineralocorticoid effector mechanism in the <cell_type> HML </cell_type> of patients with essential hypertension ."
  },
  {
    "input_text": "[ Differential diagnostic value of receptors of 1,25-dihydroxyvitamin D3 ( calcitriol ) determination in lymphocytes of children with rickets and rickets -like diseases ]",
    "target_text": "[ Differential diagnostic value of receptors of 1,25-dihydroxyvitamin D3 ( calcitriol ) determination in <cell_type> lymphocytes </cell_type> of children with rickets and rickets -like diseases ]"
  },
  {
    "input_text": "The authors provide the results of studying 1,25-dihydroxyvitamin D3 ( calcitriol ) in lymphocytes of children with rickets and rickets -like diseases .",
    "target_text": "The authors provide the results of studying 1,25-dihydroxyvitamin D3 ( calcitriol ) in <cell_type> lymphocytes </cell_type> of children with rickets and rickets -like diseases ."
  },
  {
    "input_text": "It is proposed that the character of their expression under the influence of vitamin D may be used with differential diagnostic purposes in view .",
    "target_text": "It is proposed that the character of their expression under the influence of vitamin D may be used with differential diagnostic purposes in view ."
  },
  {
    "input_text": "Regulation of gene expression with double-stranded phosphorothioate oligonucleotides .",
    "target_text": "Regulation of gene expression with double-stranded phosphorothioate oligonucleotides ."
  },
  {
    "input_text": "Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation .",
    "target_text": "Alteration of gene transcription by inhibition of specific <protein> transcriptional regulatory proteins </protein> is necessary for determining how these factors participate in cellular differentiation ."
  },
  {
    "input_text": "The functions of these proteins can be antagonized by several methods , each with specific limitations .",
    "target_text": "The functions of these proteins can be antagonized by several methods , each with specific limitations ."
  },
  {
    "input_text": "Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded ( ds ) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences .",
    "target_text": "Inhibition of <protein> sequence-specific DNA-binding proteins </protein> was achieved with double-stranded ( ds ) phosphorothioate oligonucleotides that contained octamer or kappa B consensus sequences ."
  },
  {
    "input_text": "The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor ( NF ) -kappa B .",
    "target_text": "The phosphorothioate oligonucleotides specifically bound either <protein> octamer transcription factor </protein> or <protein> nuclear factor ( NF ) -kappa B </protein> ."
  },
  {
    "input_text": "The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner .",
    "target_text": "The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner ."
  },
  {
    "input_text": "Octamer-dependent activation of a reporter plasmid or NF-kappa B -dependent activation of the human immunodeficiency virus ( HIV ) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line .",
    "target_text": "Octamer-dependent activation of a <DNA> reporter plasmid </DNA> or <protein> NF-kappa B </protein> -dependent activation of the <DNA> human immunodeficiency virus ( HIV ) enhancer </DNA> was inhibited when the appropriate phosphorothioate oligonucleotide was added to a <cell_line> transiently transfected B cell line </cell_line> ."
  },
  {
    "input_text": "Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 ( IL-2 ) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer .",
    "target_text": "Addition of phosphorothioate oligonucleotides that contained the <DNA> octamer consensus </DNA> to <cell_line> Jurkat T leukemia cells </cell_line> inhibited <protein> interleukin-2 </protein> ( <protein> IL-2 </protein> ) secretion to a degree similar to that observed with a <DNA> mutated octamer site </DNA> in the <DNA> IL-2 enhancer </DNA> ."
  },
  {
    "input_text": "The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral , immunosuppressive , or other therapeutic effects .",
    "target_text": "The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral , immunosuppressive , or other therapeutic effects ."
  },
  {
    "input_text": "[ Effect of the regimen of kidney-tonifying and qi-invigorating on aging changes of glucocorticoid receptor ]",
    "target_text": "[ Effect of the regimen of kidney-tonifying and qi-invigorating on aging changes of <protein> glucocorticoid receptor </protein> ]"
  },
  {
    "input_text": "The plasma cortisol concentration and the sites of glucocorticoid receptor ( GCR ) in the peripheral lymphocytes were measured in 32 healthy aged persons and 13 young adults .",
    "target_text": "The plasma cortisol concentration and the sites of <protein> glucocorticoid receptor </protein> ( <protein> GCR </protein> ) in the <cell_type> peripheral <cell_type> lymphocytes </cell_type> </cell_type> were measured in 32 healthy aged persons and 13 young adults ."
  },
  {
    "input_text": "In animal experiment , GCR of spleen lymphocytic cell was also measured in 18 aged rats and 9 young rats .",
    "target_text": "In animal experiment , <protein> GCR </protein> of <cell_type> spleen lymphocytic cell </cell_type> was also measured in 18 aged rats and 9 young rats ."
  },
  {
    "input_text": "The results showed that GCR was significantly lower in the aged persons or rats than that in the young while the plasma cortisol level did n't change with aging .",
    "target_text": "The results showed that <protein> GCR </protein> was significantly lower in the aged persons or rats than that in the young while the plasma cortisol level did n't change with aging ."
  },
  {
    "input_text": "So we think that GCR is more sensitive than the plasma cortisol level to reflect the aging change of the adrenal cortex function .",
    "target_text": "So we think that <protein> GCR </protein> is more sensitive than the plasma cortisol level to reflect the aging change of the adrenal cortex function ."
  },
  {
    "input_text": "After the treatment with the regimen of Kidney-tonifying and Qi-invigorating , the GCR of the aged persons and rats was enhanced , and in this way , the function of the aged adrenal cortex was improved .",
    "target_text": "After the treatment with the regimen of Kidney-tonifying and Qi-invigorating , the <protein> GCR </protein> of the aged persons and rats was enhanced , and in this way , the function of the aged adrenal cortex was improved ."
  },
  {
    "input_text": "Interferon affects nuclear proteins in cells of clinically sensitive chronic myelogenous leukemia patients .",
    "target_text": "Interferon affects <protein> nuclear proteins </protein> in cells of clinically sensitive chronic myelogenous leukemia patients ."
  },
  {
    "input_text": "Cytoplasmic protein extracts from chronic myelogenous leukemia ( CML ) cells contained an activity that altered the electrophoretic mobility of complexes formed between nuclear proteins and the transcriptional enhancers of interferon ( IFN ) -inducible genes .",
    "target_text": "Cytoplasmic protein extracts from <cell_type> chronic myelogenous leukemia ( CML ) cells </cell_type> contained an activity that altered the electrophoretic mobility of complexes formed between <protein> nuclear proteins </protein> and the transcriptional enhancers of interferon ( IFN ) -inducible genes ."
  },
  {
    "input_text": "Exposure of CML cells to IFN-alpha diminished the effect of the CML cytoplasmic proteins on these nuclear protein-DNA complexes .",
    "target_text": "Exposure of <cell_type> CML cells </cell_type> to <protein> IFN-alpha </protein> diminished the effect of the <protein> CML cytoplasmic proteins </protein> on these <protein> nuclear protein-DNA complexes </protein> ."
  },
  {
    "input_text": "The presence of clinical responsiveness to IFN-alpha correlated with the sensitivity to the IFN -induced change in the electrophoretic mobility of nuclear protein-DNA complexes .",
    "target_text": "The presence of clinical responsiveness to <protein> IFN-alpha </protein> correlated with the sensitivity to the <protein> IFN </protein> -induced change in the electrophoretic mobility of <protein> nuclear protein-DNA complexes </protein> ."
  },
  {
    "input_text": "These data suggest that the action of IFN-alpha in CML may be linked to a pathway that can result in posttranslational modification of nuclear proteins .",
    "target_text": "These data suggest that the action of <protein> IFN-alpha </protein> in CML may be linked to a pathway that can result in posttranslational modification of <protein> nuclear proteins </protein> ."
  },
  {
    "input_text": "Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1 .",
    "target_text": "<protein> Epstein-Barr virus nuclear antigen 2 </protein> transactivates <protein> latent membrane protein </protein> <protein> LMP1 </protein> ."
  },
  {
    "input_text": "Several lines of evidence are compatible with the hypothesis that Epstein-Barr virus ( EBV ) nuclear antigen 2 ( EBNA-2 ) or leader protein ( EBNA-LP ) affects expression of the EBV latent infection membrane protein LMP1 .",
    "target_text": "Several lines of evidence are compatible with the hypothesis that <protein> Epstein-Barr virus ( EBV ) nuclear antigen 2 </protein> ( <protein> EBNA-2 </protein> ) or <protein> leader protein </protein> ( <protein> EBNA-LP </protein> ) affects expression of the <protein> EBV latent infection membrane protein </protein> <protein> LMP1 </protein> ."
  },
  {
    "input_text": "We now demonstrate the following .",
    "target_text": "We now demonstrate the following ."
  },
  {
    "input_text": "( i ) Acute transfection and expression of EBNA-2 under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased LMP1 expression in P3HR-1-infected Burkitt 's lymphoma cells and the P3HR-1 or Daudi cell line .",
    "target_text": "( i ) Acute transfection and expression of <protein> EBNA-2 </protein> under control of simian virus 40 or Moloney murine leukemia virus promoters resulted in increased <protein> LMP1 </protein> expression in <cell_line> P3HR-1-infected Burkitt 's lymphoma cells </cell_line> and the <cell_line> P3HR-1 </cell_line> or <cell_line> Daudi cell line </cell_line> ."
  },
  {
    "input_text": "( ii ) Transfection and expression of EBNA-LP alone had no effect on LMP1 expression and did not act synergistically with EBNA-2 to affect LMP1 expression .",
    "target_text": "( ii ) Transfection and expression of <protein> EBNA-LP </protein> alone had no effect on <protein> LMP1 </protein> expression and did not act synergistically with <protein> EBNA-2 </protein> to affect <protein> LMP1 </protein> expression ."
  },
  {
    "input_text": "( iii ) LMP1 expression in Daudi and P3HR-1-infected cells was controlled at the mRNA level , and EBNA-2 expression in Daudi cells increased LMP1 mRNA .",
    "target_text": "( iii ) <protein> LMP1 </protein> expression in <cell_line> Daudi </cell_line> and <cell_line> P3HR-1-infected cells </cell_line> was controlled at the <RNA> mRNA </RNA> level , and <protein> EBNA-2 </protein> expression in <cell_line> Daudi cells </cell_line> increased <RNA> <protein> LMP1 </protein> mRNA </RNA> ."
  },
  {
    "input_text": "( iv ) No other EBV genes were required for EBNA-2 transactivation of LMP1 since cotransfection of recombinant EBNA-2 expression vectors and genomic LMP1 DNA fragments enhanced LMP1 expression in the EBV-negative B-lymphoma cell lines BJAB , Louckes , and BL30 .",
    "target_text": "( iv ) No other <DNA> EBV genes </DNA> were required for <protein> EBNA-2 </protein> transactivation of <protein> LMP1 </protein> since cotransfection of <DNA> recombinant <protein> EBNA-2 </protein> expression vectors </DNA> and genomic <DNA> <protein> LMP1 </protein> DNA fragments </DNA> enhanced <protein> LMP1 </protein> expression in the <cell_line> EBV-negative B-lymphoma cell lines </cell_line> <cell_line> BJAB </cell_line> , <cell_line> Louckes </cell_line> , and <cell_line> BL30 </cell_line> ."
  },
  {
    "input_text": "( v ) An EBNA-2 -responsive element was found within the -512 to +40 LMP1 DNA since this DNA linked to a chloramphenicol acetyltransferase reporter gene was transactivated by cotransfection with an EBNA-2 expression vector .",
    "target_text": "( v ) An <DNA> <protein> EBNA-2 </protein> -responsive element </DNA> was found within the <DNA> -512 to +40 <DNA> <protein> LMP1 </protein> DNA </DNA> </DNA> since this DNA linked to a <DNA> <protein> chloramphenicol acetyltransferase </protein> reporter gene </DNA> was transactivated by cotransfection with an <DNA> <protein> EBNA-2 </protein> expression vector </DNA> ."
  },
  {
    "input_text": "( vi ) The EBV type 2 EBNA-2 transactivated LMP1 as well as the EBV type 1 EBNA-2 .",
    "target_text": "( vi ) The EBV type 2 <protein> EBNA-2 </protein> transactivated <protein> LMP1 </protein> as well as the <protein> EBV type 1 <protein> EBNA-2 </protein> </protein> ."
  },
  {
    "input_text": "( vii ) Two deletions within the EBNA-2 gene which rendered EBV transformation incompetent did not transactivate LMP1 , whereas a transformation-competent EBNA-2 deletion mutant did transactivate LMP1 .",
    "target_text": "( vii ) Two deletions within the <protein> EBNA-2 </protein> gene which rendered EBV transformation incompetent did not transactivate <protein> LMP1 </protein> , whereas a <DNA> transformation-competent <protein> EBNA-2 </protein> deletion mutant </DNA> did transactivate <protein> LMP1 </protein> ."
  },
  {
    "input_text": "LMP1 is a potent effector of B-lymphocyte activation and can act synergistically with EBNA-2 to induce cellular CD23 gene expression .",
    "target_text": "<protein> LMP1 </protein> is a potent effector of B-lymphocyte activation and can act synergistically with <protein> EBNA-2 </protein> to induce cellular CD23 gene expression ."
  },
  {
    "input_text": "Thus , EBNA-2 transactivation of LMP1 amplifies the biological impact of EBNA-2 and underscores its central role in EBV-induced growth transformation .",
    "target_text": "Thus , <protein> EBNA-2 </protein> transactivation of <protein> LMP1 </protein> amplifies the biological impact of <protein> EBNA-2 </protein> and underscores its central role in EBV-induced growth transformation ."
  },
  {
    "input_text": "The expression of c-fos , c-jun , and c-myc genes is regulated by heat shock in human lymphoid cells .",
    "target_text": "The expression of <DNA> c-fos </DNA> , <DNA> c-jun </DNA> , and <DNA> c-myc genes </DNA> is regulated by heat shock in <cell_type> human lymphoid cells </cell_type> ."
  },
  {
    "input_text": "The effect of heat shock on the expression of the nuclear protooncogenes c-fos , c-jun , and c-myc was studied in human lymphoid cells .",
    "target_text": "The effect of heat shock on the expression of the <DNA> nuclear protooncogenes </DNA> <DNA> c-fos </DNA> , <DNA> c-jun </DNA> , and <DNA> c-myc </DNA> was studied in <cell_type> human lymphoid cells </cell_type> ."
  },
  {
    "input_text": "Heat shock caused an increase in c-fos and c-jun mRNA levels and a decrease in c-myc mRNA levels in pre-B ( Hyon ) and T ( DND-41 ) cell lines as well as in freshly isolated normal human thymocytes .",
    "target_text": "Heat shock caused an increase in c-fos and c-jun mRNA levels and a decrease in <RNA> <DNA> c-myc </DNA> mRNA </RNA> levels in pre-B ( Hyon ) and T ( DND-41 ) cell lines as well as in freshly isolated normal human thymocytes ."
  },
  {
    "input_text": "The changes in the mRNA levels of these protooncogenes in Hyon cells were most pronounced at 42 and 43 degrees C ; kinetic analysis demonstrated that the changes could be detected within 30 min of heat shock .",
    "target_text": "The changes in the mRNA levels of these <DNA> protooncogenes </DNA> in <cell_line> Hyon cells </cell_line> were most pronounced at 42 and 43 degrees C ; kinetic analysis demonstrated that the changes could be detected within 30 min of heat shock ."
  },
  {
    "input_text": "Altered transcription of c-fos and c-myc genes was the primary effect of heat shock .",
    "target_text": "Altered transcription of <DNA> c-fos </DNA> and <DNA> <DNA> c-myc </DNA> genes </DNA> was the primary effect of heat shock ."
  },
  {
    "input_text": "Secondarily , heat shock of Hyon cells stabilized the c-myc mRNA level by increasing its half-life from 24 to 45 min .",
    "target_text": "Secondarily , heat shock of <cell_line> Hyon cells </cell_line> stabilized the <RNA> <DNA> c-myc </DNA> mRNA </RNA> level by increasing its half-life from 24 to 45 min ."
  },
  {
    "input_text": "The overall effect of heat shock on c-myc mRNA level , however , was a marked inhibition of its transcription .",
    "target_text": "The overall effect of heat shock on <RNA> <DNA> c-myc </DNA> mRNA </RNA> level , however , was a marked inhibition of its transcription ."
  },
  {
    "input_text": "These results demonstrate that the transcription of nuclear protooncogenes is regulated by heat shock indicating a role for nuclear protooncogenes in the stress response of lymphoid cells .",
    "target_text": "These results demonstrate that the transcription of <DNA> nuclear <DNA> protooncogenes </DNA> </DNA> is regulated by heat shock indicating a role for <DNA> nuclear <DNA> protooncogenes </DNA> </DNA> in the stress response of <cell_type> lymphoid cells </cell_type> ."
  },
  {
    "input_text": "Mapping of B-cell epitopes of the human hepatitis B virus X protein .",
    "target_text": "Mapping of <protein> B-cell epitopes </protein> of the <protein> human hepatitis B virus X protein </protein> ."
  },
  {
    "input_text": "The immune response to the X protein of human hepatitis B virus ( HBV ) was studied by epitope mapping by using a set of MS2-HBx fusion proteins and synthetic peptides .",
    "target_text": "The immune response to the <protein> X protein </protein> of human hepatitis B virus ( HBV ) was studied by epitope mapping by using a set of <protein> MS2-HBx fusion proteins </protein> and synthetic peptides ."
  },
  {
    "input_text": "Antibodies in sera of patients with acute and chronic HBV infection showed a multispecific immune response .",
    "target_text": "Antibodies in sera of patients with acute and chronic HBV infection showed a multispecific immune response ."
  },
  {
    "input_text": "Each serum contained antibodies to a different set of epitopes , which taken together cover most of the HBx sequence .",
    "target_text": "Each serum contained <protein> antibodies </protein> to a different set of <protein> epitopes </protein> , which taken together cover most of the <protein> HBx sequence </protein> ."
  },
  {
    "input_text": "Some of the epitopes were detectable only by immunoblotting with fusion proteins ; others were detectable only by an enzyme-linked immunosorbent assay ( ELISA ) with synthetic peptides .",
    "target_text": "Some of the epitopes were detectable only by immunoblotting with <protein> fusion proteins </protein> ; others were detectable only by an enzyme-linked immunosorbent assay ( ELISA ) with synthetic peptides ."
  },
  {
    "input_text": "The carboxy-terminal half of the HBx protein was preferentially recognized by antibodies from patients with chronic hepatitis and contained a short immunodominant antigenic region with at least two major nonoverlapping epitopes .",
    "target_text": "The <protein> carboxy-terminal half </protein> of the <protein> <protein> HBx </protein> protein </protein> was preferentially recognized by <protein> antibodies </protein> from patients with chronic hepatitis and contained a short <protein> immunodominant antigenic region </protein> with at least two major <protein> nonoverlapping epitopes </protein> ."
  },
  {
    "input_text": "Anti- HBx antibody titers as revealed by peptide ELISAs were highest and most frequent in patients with chronic hepatitis and usually low in acutely infected patients and asymptomatic carriers .",
    "target_text": "Anti- <protein> HBx </protein> antibody titers as revealed by peptide ELISAs were highest and most frequent in patients with chronic hepatitis and usually low in acutely infected patients and asymptomatic carriers ."
  },
  {
    "input_text": "The data demonstrate a remarkable qualitative and quantitative heterogeneity of the humoral HBx immune response which can be monitored by HBx -specific peptide ELISAs .",
    "target_text": "The data demonstrate a remarkable qualitative and quantitative heterogeneity of the humoral <protein> HBx </protein> immune response which can be monitored by <protein> HBx </protein> -specific peptide ELISAs ."
  },
  {
    "input_text": "Such tests may become useful diagnostic tools .",
    "target_text": "Such tests may become useful diagnostic tools ."
  },
  {
    "input_text": "[ The inhibitory effect of hydrocortisone on the chemotactic migration of human leukocytes ]",
    "target_text": "[ The inhibitory effect of hydrocortisone on the chemotactic migration of <cell_type> human leukocytes </cell_type> ]"
  },
  {
    "input_text": "Random migration ( RM ) and chemotactic migration ( ChtM ) of human leukocytes to yeast activated serum were studied with the modified Boyden chamber method .",
    "target_text": "Random migration ( RM ) and chemotactic migration ( ChtM ) of <cell_type> human leukocytes </cell_type> to yeast activated serum were studied with the modified Boyden chamber method ."
  },
  {
    "input_text": "Both RM and ChtM showed circadian rhythm .",
    "target_text": "Both RM and ChtM showed circadian rhythm ."
  },
  {
    "input_text": "Leukocytes migrated most rapidly at night .",
    "target_text": "<cell_type> Leukocytes </cell_type> migrated most rapidly at night ."
  },
  {
    "input_text": "The difference between the peak ( 0 : 00 ) and trough values ( 8 : 00 ) of RM and ChtM was significant statistically ( P less than 0.01 ) .",
    "target_text": "The difference between the peak ( 0 : 00 ) and trough values ( 8 : 00 ) of RM and ChtM was significant statistically ( P less than 0.01 ) ."
  },
  {
    "input_text": "ChtM was inhibited by hydrocortisone ( F ) of physiological concentration ( 10 ( -9 ) -10 ( -7 ) mol/L ) which was dose-dependent and completely antagonized by the competitive antagonist , RU38486 .",
    "target_text": "ChtM was inhibited by hydrocortisone ( F ) of physiological concentration ( 10 ( -9 ) -10 ( -7 ) mol/L ) which was dose-dependent and completely antagonized by the competitive antagonist , RU38486 ."
  },
  {
    "input_text": "The inhibitory effect was much more evident with higher dose ( more than 10 ( -5 ) mol/L ) and it was also reversed by RU38486 , but only partially .",
    "target_text": "The inhibitory effect was much more evident with higher dose ( more than 10 ( -5 ) mol/L ) and it was also reversed by RU38486 , but only partially ."
  },
  {
    "input_text": "It is suggested that glucocorticoids ( GC ) may be a physiological regulator of the activity of leukocytes and its inhibitory action on ChtM may be involved in antiinflammatory mechanisms of GC of pharmacological doses .",
    "target_text": "It is suggested that glucocorticoids ( GC ) may be a physiological regulator of the activity of <cell_type> leukocytes </cell_type> and its inhibitory action on ChtM may be involved in antiinflammatory mechanisms of GC of pharmacological doses ."
  },
  {
    "input_text": "The action of physiological and pharmacological concentration of GC may be mediated by low affinity specific binding sites of glucocorticoid receptors .",
    "target_text": "The action of physiological and pharmacological concentration of GC may be mediated by <protein> low affinity specific binding sites </protein> of <protein> glucocorticoid receptors </protein> ."
  },
  {
    "input_text": "Heterogeneity of antigen molecules recognized by anti-tax1 monoclonal antibody Lt-4 in cell lines bearing human T cell leukemia virus type I and related retroviruses .",
    "target_text": "Heterogeneity of <protein> antigen molecules </protein> recognized by <protein> anti-tax1 monoclonal antibody </protein> <protein> Lt-4 </protein> in cell lines bearing human T cell leukemia virus type I and related retroviruses ."
  },
  {
    "input_text": "Using a monoclonal antibody , Lt-4 , directed against human T cell leukemia virus type I ( HTLV-I ) trans-activator ( tax1 ) antigen , we examined the expression of tax1 and related antigens in a variety of T cell lines bearing HTLV-I and related retroviruses , simian T cell leukemia virus type I ( STLV-I ) and HTLV-II , by immunofluorescence and immunoblot assays .",
    "target_text": "Using a <protein> monoclonal antibody </protein> , <protein> Lt-4 </protein> , directed against <protein> <protein> human T cell leukemia virus type I ( HTLV-I ) trans-activator </protein> ( <protein> tax1 </protein> ) antigen </protein> , we examined the expression of <protein> tax1 </protein> and related <protein> antigens </protein> in a variety of <cell_line> T cell lines </cell_line> bearing HTLV-I and related retroviruses , simian T cell leukemia virus type I ( STLV-I ) and HTLV-II , by immunofluorescence and immunoblot assays ."
  },
  {
    "input_text": "Lt-4 reacted with all HTLV-I -bearing cell lines tested and five out of eight simian cell lines bearing STLV-I , but not with an HTLV-II -bearing cell line .",
    "target_text": "<protein> Lt-4 </protein> reacted with all <cell_line> HTLV-I -bearing cell lines </cell_line> tested and five out of eight <cell_line> simian cell lines </cell_line> bearing STLV-I , but not with an <cell_line> HTLV-II -bearing cell line </cell_line> ."
  },
  {
    "input_text": "Lt-4 detected 40 kd tax1 antigen molecules in most HTLV-I -bearing cell lines except one cell line that expressed 39 kd tax1 antigen .",
    "target_text": "<protein> Lt-4 </protein> detected 40 kd <protein> <protein> tax1 </protein> antigen molecules </protein> in most <cell_line> HTLV-I -bearing cell lines </cell_line> except one cell line that expressed <protein> 39 kd <protein> tax1 </protein> antigen </protein> ."
  },
  {
    "input_text": "In the STLV-I -bearing T cell lines , tax1 -related antigen molecules detected by Lt-4 were heterogeneous , having molecular weights in the range of 36-41 kd .",
    "target_text": "In the <cell_line> STLV-I -bearing <cell_line> T cell lines </cell_line> </cell_line> , <protein> <protein> tax1 </protein> -related antigen molecules </protein> detected by <protein> Lt-4 </protein> were heterogeneous , having molecular weights in the range of 36-41 kd ."
  },
  {
    "input_text": "Characterization of the human immunodeficiency virus type 1 enhancer -binding proteins from the human T-cell line Jurkat .",
    "target_text": "Characterization of the <protein> <DNA> human immunodeficiency virus type 1 enhancer </DNA> -binding proteins </protein> from the <cell_line> human T-cell line </cell_line> <cell_line> Jurkat </cell_line> ."
  },
  {
    "input_text": "The transcription of the human immunodeficiency virus type 1 ( HIV-1 ) is under the control of cellular proteins that bind to the viral long terminal repeat ( LTR ) .",
    "target_text": "The transcription of the human immunodeficiency virus type 1 ( HIV-1 ) is under the control of <protein> cellular proteins </protein> that bind to the <DNA> viral long terminal repeat </DNA> ( <DNA> LTR </DNA> ) ."
  },
  {
    "input_text": "Among the protein-binding regions of the HIV-1 LTR is the transcription-enhancer region .",
    "target_text": "Among the protein-binding regions of the <DNA> HIV-1 LTR </DNA> is the <DNA> transcription-enhancer region </DNA> ."
  },
  {
    "input_text": "We show that at least one inducible , C1 , and one constitutive , C2 , protein can bind to the HIV enhancer in Jurkat cells .",
    "target_text": "We show that at least one <protein> inducible </protein> , <protein> C1 </protein> , and one <protein> constitutive , <protein> C2 </protein> , protein </protein> can bind to the <DNA> HIV enhancer </DNA> in <cell_line> Jurkat cells </cell_line> ."
  },
  {
    "input_text": "The two proteins differ in their surface charge , since they are separable by anion-exchange chromatography .",
    "target_text": "The two proteins differ in their surface charge , since they are separable by anion-exchange chromatography ."
  },
  {
    "input_text": "Bivalent cations such as Mg2+ and Zn2+ differentially affect their binding to oligonucleotides which contain the HIV-enhancer domain .",
    "target_text": "Bivalent cations such as Mg2+ and Zn2+ differentially affect their binding to oligonucleotides which contain the <DNA> HIV-enhancer domain </DNA> ."
  },
  {
    "input_text": "Both C1 and C2 proteins also bind to a similar sequence found in the interleukin-2 -receptor alpha-subunit enhancer .",
    "target_text": "Both <protein> C1 </protein> and <protein> C2 proteins </protein> also bind to a similar sequence found in the <DNA> <protein> <protein> interleukin-2 </protein> -receptor alpha-subunit </protein> enhancer </DNA> ."
  },
  {
    "input_text": "The inducible C1 protein was partially purified by three chromatographic steps and characterized by u.v. cross-linking as a 47 kDa protein .",
    "target_text": "The <protein> inducible <protein> C1 </protein> protein </protein> was partially purified by three chromatographic steps and characterized by u.v. cross-linking as a <protein> 47 kDa protein </protein> ."
  },
  {
    "input_text": "Differences in transcriptional enhancers of HIV-1 and HIV-2 .",
    "target_text": "Differences in <DNA> transcriptional enhancers </DNA> of HIV-1 and HIV-2 ."
  },
  {
    "input_text": "Response to T cell activation signals .",
    "target_text": "Response to <cell_type> T cell </cell_type> activation signals ."
  },
  {
    "input_text": "T cell activation results in high levels of HIV replication and is thought to be one mechanism leading to the conversion from latent to active viral infection .",
    "target_text": "<cell_type> T cell </cell_type> activation results in high levels of HIV replication and is thought to be one mechanism leading to the conversion from latent to active viral infection ."
  },
  {
    "input_text": "In HIV-1 , the sequences that respond to these signaling events are found in the long terminal repeat ( LTR ) and comprise the transcriptional enhancer , which contains two conserved binding sites for the nuclear factor kappa B ( NF kappa B ) .",
    "target_text": "In HIV-1 , the sequences that respond to these signaling events are found in the <DNA> long terminal repeat </DNA> ( <DNA> LTR </DNA> ) and comprise the <DNA> transcriptional enhancer </DNA> , which contains two <DNA> conserved binding sites </DNA> for the <protein> nuclear factor kappa B </protein> ( <protein> NF kappa B </protein> ) ."
  },
  {
    "input_text": "The corresponding region in the second AIDS retrovirus , HIV-2 , contains a conserved and a divergent NF kappa B binding site .",
    "target_text": "The corresponding region in the second AIDS retrovirus , HIV-2 , contains a conserved and a divergent <DNA> <protein> NF kappa B </protein> binding site </DNA> ."
  },
  {
    "input_text": "We demonstrate that the HIV-1 LTR responds better than the HIV-2 LTR to T cell activation signals .",
    "target_text": "We demonstrate that the <DNA> HIV-1 LTR </DNA> responds better than the <DNA> HIV-2 LTR </DNA> to T cell activation signals ."
  },
  {
    "input_text": "These qualitative differences in the response to T cell activation are reproduced not only when HIV-1 or HIV-2 enhancers are placed upstream of a heterologous promoter but also when these enhancers are switched between their respective LTR .",
    "target_text": "These qualitative differences in the response to <cell_type> T cell </cell_type> activation are reproduced not only when HIV-1 or HIV-2 enhancers are placed upstream of a <DNA> heterologous promoter </DNA> but also when these <DNA> enhancers </DNA> are switched between their respective <DNA> LTR </DNA> ."
  },
  {
    "input_text": "In electrophoretic mobility shift assays , NF kappa B binds to both conserved sites in the HIV-1 transcriptional enhancer and only to the single conserved site in the HIV-2 transcriptional enhancer .",
    "target_text": "In electrophoretic mobility shift assays , <protein> NF kappa B </protein> binds to both conserved sites in the <DNA> HIV-1 transcriptional enhancer </DNA> and only to the single conserved site in the <DNA> HIV-2 transcriptional enhancer </DNA> ."
  },
  {
    "input_text": "Instead of NF kappa B , the activator protein 3 binds to the divergent site in HIV-2 .",
    "target_text": "Instead of <protein> NF kappa B </protein> , the <protein> activator protein 3 </protein> binds to the divergent site in HIV-2 ."
  },
  {
    "input_text": "In conclusion , HIV-1 and HIV-2 are differentially regulated by T cell activation signals , and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV-1 infection .",
    "target_text": "In conclusion , HIV-1 and HIV-2 are differentially regulated by T cell activation signals , and this difference may account for the longer period of viral latency observed with HIV-2 than with HIV-1 infection ."
  },
  {
    "input_text": "NF-X2 that binds to the DRA X2-box is activator protein 1 .",
    "target_text": "<protein> NF-X2 </protein> that binds to the <DNA> DRA X2-box </DNA> is <protein> activator protein 1 </protein> ."
  },
  {
    "input_text": "Expression cloning of c-Jun .",
    "target_text": "Expression cloning of <protein> c-Jun </protein> ."
  },
  {
    "input_text": "Human class II MHC Ag are a family of cell surface glycoproteins .",
    "target_text": "<protein> Human class II MHC Ag </protein> are a family of <protein> cell surface glycoproteins </protein> ."
  },
  {
    "input_text": "Their constitutive expression is limited to B lymphocytes and thymic epithelial cells .",
    "target_text": "Their constitutive expression is limited to <cell_type> B lymphocytes </cell_type> and <cell_type> thymic epithelial cells </cell_type> ."
  },
  {
    "input_text": "In many other cells their expression can be induced by IFN-gamma .",
    "target_text": "In many other cells their expression can be induced by <protein> IFN-gamma </protein> ."
  },
  {
    "input_text": "Conserved upstream promoter sequences regulate this tissue-specific expression of class II genes .",
    "target_text": "Conserved upstream promoter sequences regulate this tissue-specific expression of <DNA> class II genes </DNA> ."
  },
  {
    "input_text": "In the DRA promoter , one of these cis-acting regulatory motifs is the X2-box to which nuclear factor X2 ( NF-X2 ) binds .",
    "target_text": "In the <DNA> DRA promoter </DNA> , one of these <DNA> cis-acting regulatory motifs </DNA> is the <DNA> X2-box </DNA> to which <protein> nuclear factor X2 </protein> ( <protein> NF-X2 </protein> ) binds ."
  },
  {
    "input_text": "Here , we present the isolation and characterization of the full-length cDNA clone encoding NF-X2 .",
    "target_text": "Here , we present the isolation and characterization of the <DNA> full-length cDNA clone </DNA> encoding <protein> NF-X2 </protein> ."
  },
  {
    "input_text": "This cDNA clone was isolated by expression cDNA cloning , and encodes the human c-Jun protein , which together with c-Fos forms the heterodimeric activator protein-1 transcription complex .",
    "target_text": "This <DNA> cDNA clone </DNA> was isolated by expression <DNA> cDNA </DNA> cloning , and encodes the <protein> human <protein> c-Jun </protein> protein </protein> , which together with <protein> c-Fos </protein> forms the <protein> heterodimeric activator protein-1 transcription complex </protein> ."
  },
  {
    "input_text": "Whereas c-Fos /c-Jun heterodimers do not exist in B cells , they form and bind to the X2-box in class II nonexpressing cells .",
    "target_text": "Whereas <protein> <protein> c-Fos </protein> <protein> /c-Jun </protein> heterodimers </protein> do not exist in <cell_line> B cells </cell_line> , they form and bind to the <DNA> X2-box </DNA> in <cell_line> class II nonexpressing cells </cell_line> ."
  },
  {
    "input_text": "Thus , c-Fos /c-Jun heterodimers might contribute to the repression of DRA gene expression .",
    "target_text": "Thus , <protein> <protein> c-Fos </protein> <protein> /c-Jun </protein> heterodimers </protein> might contribute to the repression of <DNA> DRA gene </DNA> expression ."
  },
  {
    "input_text": "Synthesis of 4,19-disubstituted derivatives of DOC .",
    "target_text": "Synthesis of 4,19-disubstituted derivatives of DOC ."
  },
  {
    "input_text": "Radioreceptor assay of some corticosteroid derivatives in human mononuclear leukocytes .",
    "target_text": "Radioreceptor assay of some corticosteroid derivatives in <cell_type> human mononuclear leukocytes </cell_type> ."
  },
  {
    "input_text": "Several new 4,19-substituted steroids and previously synthesized corticosteroids were assayed for affinity to type 1 receptors in human mononuclear leukocytes .",
    "target_text": "Several new 4,19-substituted steroids and previously synthesized corticosteroids were assayed for affinity to <protein> type 1 receptors </protein> in <cell_type> human mononuclear leukocytes </cell_type> ."
  },
  {
    "input_text": "11 beta,19-epoxy-4,21-dihydroxypregn-4-ene-3,20-dione ( 2 ) was hydrogenated with Pd-C to yield a mixture of all four dihydro derivatives 5 , accompanied by 4,21-diacetoxy-11 beta,19-epoxy-3-hydroxypregnan-20-one ( 6 ) and 21-acetoxy-11 beta,19-epoxy-4-hydroxypregnane-3,20-dione ( 7 ) .",
    "target_text": "11 beta,19-epoxy-4,21-dihydroxypregn-4-ene-3,20-dione ( 2 ) was hydrogenated with Pd-C to yield a mixture of all four dihydro derivatives 5 , accompanied by 4,21-diacetoxy-11 beta,19-epoxy-3-hydroxypregnan-20-one ( 6 ) and 21-acetoxy-11 beta,19-epoxy-4-hydroxypregnane-3,20-dione ( 7 ) ."
  },
  {
    "input_text": "With hot acetic + p-toluenesulfonic acid 5 underwent rearrangement to 21-acetoxy-11 beta,19-epoxypregn-5-ene-4,20-dione ( 8 ) Pd-C hydrogenation of 3,21-diacetoxy-5 beta,19-cyclopregna-2,9(11)-diene-4,20-dione ( 10 ) gave 3,21-diacetoxy-5 beta,19-cyclopregn-5-ene-4,20-dione ( 11 ) and the 9,11-dihydro derivative of the latter .",
    "target_text": "With hot acetic + p-toluenesulfonic acid 5 underwent rearrangement to 21-acetoxy-11 beta,19-epoxypregn-5-ene-4,20-dione ( 8 ) Pd-C hydrogenation of 3,21-diacetoxy-5 beta,19-cyclopregna-2,9(11)-diene-4,20-dione ( 10 ) gave 3,21-diacetoxy-5 beta,19-cyclopregn-5-ene-4,20-dione ( 11 ) and the 9,11-dihydro derivative of the latter ."
  },
  {
    "input_text": "Treatment of 10 with warm HCl furnished 19-chloro-4,21-dihydroxypregna-4,9(11)-diene-3,20-dione (13) .",
    "target_text": "Treatment of 10 with warm HCl furnished 19-chloro-4,21-dihydroxypregna-4,9(11)-diene-3,20-dione (13) ."
  },
  {
    "input_text": "Pd-C hydrogenation of its diacetate 14 afforded the 4,5-dihydro derivative 18, 19-chloro-21-acetoxypregn-9(11)-en-20-one ( 15 ) , its 4-acetoxy derivative 16 and the 3,4-diacetoxy derivative 17 .",
    "target_text": "Pd-C hydrogenation of its diacetate 14 afforded the 4,5-dihydro derivative 18, 19-chloro-21-acetoxypregn-9(11)-en-20-one ( 15 ) , its 4-acetoxy derivative 16 and the 3,4-diacetoxy derivative 17 ."
  },
  {
    "input_text": "When tested in a radioreceptor assay in human mononuclear leukocytes the synthesized compounds showed only low relative binding affinities ( RBA ) to type 1 receptor , the highest being 0.72 % for 13 ( aldosterone = 100 % ) .",
    "target_text": "When tested in a radioreceptor assay in <cell_type> human mononuclear leukocytes </cell_type> the synthesized compounds showed only low relative binding affinities ( RBA ) to <protein> type 1 receptor </protein> , the highest being 0.72 % for 13 ( aldosterone = 100 % ) ."
  },
  {
    "input_text": "For comparison , other RBA in this system were : 19-noraldosterone , 20 % ; 18-deoxyaldosterone , 5.8 % ; 18-deoxy-19-noraldosterone , 4.7 % ; 18,21-anhydroaldosterone , 0.37 % ; 17-isoaldosterone , 7.6 % and apoaldosterone , 4.3 %",
    "target_text": "For comparison , other RBA in this system were : 19-noraldosterone , 20 % ; 18-deoxyaldosterone , 5.8 % ; 18-deoxy-19-noraldosterone , 4.7 % ; 18,21-anhydroaldosterone , 0.37 % ; 17-isoaldosterone , 7.6 % and apoaldosterone , 4.3 %"
  },
  {
    "input_text": "Cell type specificity and activation requirements for NFAT-1 ( nuclear factor of activated T-cells ) transcriptional activity determined by a new method using transgenic mice to assay transcriptional activity of an individual nuclear factor .",
    "target_text": "Cell type specificity and activation requirements for <protein> NFAT-1 </protein> ( <protein> nuclear factor </protein> of <cell_type> activated T-cells </cell_type> ) transcriptional activity determined by a new method using transgenic mice to assay transcriptional activity of an individual <protein> nuclear factor </protein> ."
  },
  {
    "input_text": "Nuclear factor of activated T-cells ( NFAT-1 ) is a transcription factor which is considered to be an important regulator in early T-cell activation .",
    "target_text": "<protein> Nuclear factor </protein> of <cell_type> activated T-cells </cell_type> ( <protein> NFAT-1 </protein> ) is a <protein> transcription factor </protein> which is considered to be an important regulator in early T-cell activation ."
  },
  {
    "input_text": "We have developed a system to monitor the transcriptional activity of NFAT-1 at the single cell level in whole animals .",
    "target_text": "We have developed a system to monitor the transcriptional activity of <protein> NFAT-1 </protein> at the single cell level in whole animals ."
  },
  {
    "input_text": "The system is based on the use of an oligomerized NFAT-1 binding motif that directs transcription of SV40 T-antigen in transgenic mice .",
    "target_text": "The system is based on the use of an oligomerized <protein> NFAT-1 </protein> binding motif that directs <protein> transcription of SV40 T-antigen </protein> in transgenic mice ."
  },
  {
    "input_text": "This report represents the first demonstration that a multimerized short binding motif can function appropriately in transgenic mice .",
    "target_text": "This report represents the first demonstration that a multimerized short binding motif can function appropriately in transgenic mice ."
  },
  {
    "input_text": "NFAT-1 activity had previously been thought to be confined to activated T-lymphocytes upon release of intracellular calcium .",
    "target_text": "<protein> NFAT-1 </protein> activity had previously been thought to be confined to <cell_type> activated T-lymphocytes </cell_type> upon release of <cell_type> intracellular calcium </cell_type> ."
  },
  {
    "input_text": "By targeting NFAT-1 -dependent gene expression in transgenic mice we discovered new sites of NFAT-1 activity .",
    "target_text": "By targeting <protein> NFAT-1 </protein> -dependent gene expression in transgenic mice we discovered new sites of <protein> NFAT-1 </protein> activity ."
  },
  {
    "input_text": "Besides in T-lymphocytes NFAT-1 activity could also be induced in T-lymphocyte-depleted spleen cells and purified B-lymphocytes and requires agents that both release intracellular calcium and activate protein kinase C .",
    "target_text": "Besides in <cell_type> T-lymphocytes </cell_type> <protein> NFAT-1 </protein> activity could also be induced in <cell_type> T-lymphocyte-depleted spleen cells </cell_type> and <cell_type> purified B-lymphocytes </cell_type> and requires agents that both release intracellular calcium and activate <protein> protein kinase C </protein> ."
  },
  {
    "input_text": "A difference in the time course of appearance of NFAT-1 activity between T-lymphocytes and non-T-lymphocytes was revealed .",
    "target_text": "A difference in the time course of appearance of <protein> NFAT-1 </protein> activity between <cell_type> T-lymphocytes </cell_type> and <cell_type> non-T-lymphocytes </cell_type> was revealed ."
  },
  {
    "input_text": "Constitutive expression was observed in a small population of cells in the dermis and some mice have developed skin lesions .",
    "target_text": "Constitutive expression was observed in a small population of cells in the dermis and some mice have developed skin lesions ."
  },
  {
    "input_text": "Interestingly , the tissue pattern of expression of the NFAT-1 activity resembles the expression pattern described for HIV-LTR/tat transgenic mice ( Vogel , J. , Hinrichs , S. H. , Reynolds , R. K. , Luciw , P. A. , and Jay , G. ( 1988 ) Nature 335 , 606-611 ) .",
    "target_text": "Interestingly , the tissue pattern of expression of the <protein> NFAT-1 </protein> activity resembles the expression pattern described for HIV-LTR/tat transgenic mice ( Vogel , J. , Hinrichs , S. H. , Reynolds , R. K. , Luciw , P. A. , and Jay , G. ( 1988 ) Nature 335 , 606-611 ) ."
  },
  {
    "input_text": "This similarity in expression and the fact that NFAT-1 has been shown to bind functional sequences in HIV-LTR suggest a role for NFAT-1 in dermal activation of the HIV-LTR .",
    "target_text": "This similarity in expression and the fact that <protein> NFAT-1 </protein> has been shown to bind <DNA> functional sequences </DNA> in <DNA> HIV-LTR </DNA> suggest a role for <protein> NFAT-1 </protein> in dermal activation of the <DNA> HIV-LTR </DNA> ."
  },
  {
    "input_text": "A novel T-cell protein which recognizes a palindromic sequence in the negative regulatory element of the human immunodeficiency virus long terminal repeat .",
    "target_text": "A novel <protein> T-cell protein </protein> which recognizes a <DNA> palindromic sequence </DNA> in the <DNA> negative regulatory element </DNA> of the <DNA> human immunodeficiency virus long terminal repeat </DNA> ."
  },
  {
    "input_text": "Two major protein-binding sites within the negative regulatory element of the human immunodeficiency virus type 1 long terminal repeat have been identified .",
    "target_text": "Two <DNA> major protein-binding sites </DNA> within the <DNA> negative regulatory element </DNA> of the <DNA> human immunodeficiency virus type 1 long terminal repeat </DNA> have been identified ."
  },
  {
    "input_text": "One ( site B ) contained a palindromic sequence with homology to steroid/thyroid hormone response elements but was distinct from previously described binding sites of this class .",
    "target_text": "One ( <DNA> site B </DNA> ) contained a <DNA> palindromic sequence </DNA> with homology to <DNA> steroid/thyroid hormone response elements </DNA> but was distinct from previously described binding sites of this class ."
  },
  {
    "input_text": "A novel T-cell protein recognized the palindromic sequence within site B and also bound estrogen- or thyroid hormone- response elements with lower affinity .",
    "target_text": "A novel <protein> T-cell protein </protein> recognized the <DNA> palindromic sequence </DNA> within <DNA> site B </DNA> and also bound estrogen- or thyroid hormone- response elements with lower affinity ."
  },
  {
    "input_text": "A 7-base-pair mutation in the site B palindrome , which destroyed protein binding , resulted in increased expression from the human immunodeficiency virus type 1 long terminal repeat in T cells .",
    "target_text": "A 7-base-pair mutation in the <DNA> <DNA> site B </DNA> palindrome </DNA> , which destroyed protein binding , resulted in increased expression from the <DNA> human immunodeficiency virus type 1 long terminal repeat </DNA> in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "Progesterone suppression of pregnancy lymphocytes is not mediated by glucocorticoid effect .",
    "target_text": "Progesterone suppression of <cell_type> pregnancy lymphocytes </cell_type> is not mediated by glucocorticoid effect ."
  },
  {
    "input_text": "This study investigated whether the suppressive effect of progesterone on pregnancy lymphocytes is mediated by specific progesterone receptors .",
    "target_text": "This study investigated whether the suppressive effect of progesterone on <cell_type> pregnancy lymphocytes </cell_type> is mediated by specific <protein> progesterone receptors </protein> ."
  },
  {
    "input_text": "The effects of a competitive progesterone antagonist ( RU486 ) and a specific glucocorticoid receptor blocker ( RU43044 ) were tested on the release of a blocking factor by progesterone -treated pregnancy lymphocytes .",
    "target_text": "The effects of a competitive progesterone antagonist ( RU486 ) and a specific <protein> glucocorticoid receptor </protein> blocker ( RU43044 ) were tested on the release of a <protein> blocking factor </protein> by <cell_line> progesterone -treated <cell_type> pregnancy lymphocytes </cell_type> </cell_line> ."
  },
  {
    "input_text": "RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the blocking factor , while RU 43044 was without effect .",
    "target_text": "RU 486 tested at an equal concentration as progesterone significantly inhibited the production of the <protein> blocking factor </protein> , while RU 43044 was without effect ."
  },
  {
    "input_text": "These data suggest that in pregnancy , lymphocyte progesterone acts on specific progesterone receptors and glucocorticoid binding sites are not involved .",
    "target_text": "These data suggest that in pregnancy , lymphocyte progesterone acts on specific <protein> progesterone receptors </protein> and <protein> glucocorticoid binding sites </protein> are not involved ."
  },
  {
    "input_text": "The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90- kilodalton heat shock proteins .",
    "target_text": "The <protein> 56-59-kilodalton protein </protein> identified in <protein> untransformed steroid receptor complexes </protein> is a <protein> unique protein </protein> that exists in cytosol in a complex with both the 70- and 90- kilodalton heat shock proteins ."
  },
  {
    "input_text": "It has previously been shown that 9S , untransformed progestin , estrogen , androgen , and glucocorticoid receptor complexes in rabbit uterine and liver cytosols contain a 59-kDa protein [ Tai , P.K. , Maeda , Y. , Nakao , K. , Wakim , N.G. , Duhring , J.L. , & Faber , L.E. ( 1986 ) Biochemistry 25 , 5269-5275 ] .",
    "target_text": "It has previously been shown that <protein> 9S </protein> , untransformed progestin , estrogen , androgen , and glucocorticoid receptor complexes in rabbit uterine and liver cytosols contain a <protein> 59-kDa protein </protein> [ Tai , P.K. , Maeda , Y. , Nakao , K. , Wakim , N.G. , Duhring , J.L. , & Faber , L.E. ( 1986 ) Biochemistry 25 , 5269-5275 ] ."
  },
  {
    "input_text": "In this work we show that the monoclonal antibody KN 382/EC1 raised against the rabbit 59-kDa protein reacts with 9S , untransformed glucocorticoid receptor complexes in cytosol prepared from human IM-9 lymphocytes but not with 4S salt-transformed receptors .",
    "target_text": "In this work we show that the <protein> monoclonal antibody KN 382/EC1 </protein> raised against the <protein> rabbit 59-kDa protein </protein> reacts with <protein> 9S </protein> , <protein> untransformed glucocorticoid receptor complexes </protein> in cytosol prepared from <cell_line> human IM-9 lymphocytes </cell_line> but not with <protein> 4S salt-transformed receptors </protein> ."
  },
  {
    "input_text": "The human protein recognized by the EC1 antibody is a 56-kDa protein ( p56 ) of moderate abundance located predominantly in the cytoplasm by indirect immunofluorescence .",
    "target_text": "The human protein recognized by the <protein> EC1 antibody </protein> is a <protein> 56-kDa protein </protein> ( <protein> p56 </protein> ) of moderate abundance located predominantly in the cytoplasm by indirect immunofluorescence ."
  },
  {
    "input_text": "There are at least six isomorphs of p56 by two-dimensional gel analysis .",
    "target_text": "There are at least six <protein> isomorphs </protein> of <protein> p56 </protein> by two-dimensional gel analysis ."
  },
  {
    "input_text": "N-Terminal sequencing ( 20 amino acids ) shows that p56 is a unique human protein .",
    "target_text": "N-Terminal sequencing ( 20 amino acids ) shows that <protein> p56 </protein> is a <protein> unique human protein </protein> ."
  },
  {
    "input_text": "When p56 is immunoadsorbed from IM-9 cell cytosol , both the 70- and 90- kDa heat shock proteins are coadsorbed in an immune-specific manner .",
    "target_text": "When <protein> p56 </protein> is immunoadsorbed from <cell_line> IM-9 cell </cell_line> cytosol , both the 70- and 90- kDa heat shock proteins are coadsorbed in an immune-specific manner ."
  },
  {
    "input_text": "Neither heat shock protein reacts directly with the EC1 antibody .",
    "target_text": "Neither <protein> heat shock protein </protein> reacts directly with the <protein> EC1 antibody </protein> ."
  },
  {
    "input_text": "We conclude that p56 exists in cytosol in a higher order complex containing hsp70 and hsp90 , both of which in turn have been found to be associated with untransformed steroid receptors .",
    "target_text": "We conclude that <protein> p56 </protein> exists in cytosol in a higher order complex containing <protein> hsp70 </protein> and <protein> hsp90 </protein> , both of which in turn have been found to be associated with <protein> untransformed steroid receptors </protein> ."
  },
  {
    "input_text": "Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus .",
    "target_text": "Sequence-specific DNA binding of the <protein> proto-oncoprotein </protein> <protein> ets-1 </protein> defines a <DNA> transcriptional activator sequence </DNA> within the <DNA> long terminal repeat </DNA> of the Moloney murine sarcoma virus ."
  },
  {
    "input_text": "The ets proto-oncogene family is a group of sequence-related genes whose normal cellular function is unknown .",
    "target_text": "The <DNA> ets proto-oncogene family </DNA> is a group of <DNA> sequence-related genes </DNA> whose normal cellular function is unknown ."
  },
  {
    "input_text": "In a study of cellular proteins involved in the transcriptional regulation of murine retroviruses in T lymphocytes , we have discovered that a member of the ets gene family encodes a sequence-specific DNA-binding protein .",
    "target_text": "In a study of <protein> cellular proteins </protein> involved in the transcriptional regulation of murine retroviruses in <cell_type> T lymphocytes </cell_type> , we have discovered that a member of the <DNA> ets gene family </DNA> encodes a <protein> sequence-specific DNA-binding protein </protein> ."
  },
  {
    "input_text": "A mouse ets-1 cDNA clone was obtained by screening a mouse thymus cDNA expression library with a double-stranded oligonucleotide probe representing 20 bp of the Moloney murine sarcoma virus ( MSV ) long terminal repeat ( LTR ) .",
    "target_text": "A <DNA> mouse <protein> ets-1 </protein> cDNA clone </DNA> was obtained by screening a <DNA> mouse thymus cDNA expression library </DNA> with a <DNA> double-stranded oligonucleotide probe </DNA> representing 20 bp of the Moloney murine sarcoma virus ( MSV ) <DNA> long terminal repeat </DNA> ( <DNA> LTR </DNA> ) ."
  },
  {
    "input_text": "The cDNA sequence has an 813-bp open reading frame ( ORF ) whose predicted amino acid sequence is 97.6 % identical to the 272 carboxy-terminal amino acids of the human ets-1 protein .",
    "target_text": "The <DNA> cDNA sequence </DNA> has an <DNA> 813-bp open reading frame </DNA> ( <DNA> ORF </DNA> ) whose predicted <protein> amino acid sequence </protein> is 97.6 % identical to the <protein> 272 carboxy-terminal amino acids </protein> of the <protein> human <protein> ets-1 </protein> protein </protein> ."
  },
  {
    "input_text": "The ORF was expressed in bacteria , and the 30-kD protein product was shown to bind DNA in a sequence-specific manner by mobility-shift assays , Southwestern blot analysis , and methylation interference .",
    "target_text": "The <DNA> ORF </DNA> was expressed in bacteria , and the <protein> 30-kD protein product </protein> was shown to bind <DNA> DNA </DNA> in a sequence-specific manner by mobility-shift assays , Southwestern blot analysis , and methylation interference ."
  },
  {
    "input_text": "A mutant LTR containing four base pair substitutions in the ets-1 binding site was constructed and was shown to have reduced binding in vitro .",
    "target_text": "A <DNA> mutant LTR </DNA> containing four base pair substitutions in the <DNA> <protein> ets-1 </protein> binding site </DNA> was constructed and was shown to have reduced binding in vitro ."
  },
  {
    "input_text": "Transcriptional efficiency of the MSV LTR promoter containing this disrupted ets-1 binding site was compared to the activity of a wild-type promoter in mouse T lymphocytes in culture , and 15- to 20-fold reduction in expression of a reporter gene was observed .",
    "target_text": "Transcriptional efficiency of the <DNA> MSV LTR promoter </DNA> containing this disrupted <DNA> <protein> ets-1 </protein> binding site </DNA> was compared to the activity of a <DNA> wild-type promoter </DNA> in <cell_type> mouse <cell_type> T lymphocytes </cell_type> </cell_type> in culture , and 15- to 20-fold reduction in expression of a <DNA> reporter gene </DNA> was observed ."
  },
  {
    "input_text": "We propose that ets-1 functions as a transcriptional activator of mammalian type-C retroviruses and speculate that ets-related genes constitute a new group of eukaryotic DNA-binding proteins .",
    "target_text": "We propose that <protein> ets-1 </protein> functions as a transcriptional activator of mammalian type-C retroviruses and speculate that <DNA> ets-related genes </DNA> constitute a new group of <protein> eukaryotic DNA-binding proteins </protein> ."
  },
  {
    "input_text": "Type II estrogen binding sites in human peripheral blood mononuclear cells : variations during the menstrual cycle .",
    "target_text": "<protein> Type II estrogen binding sites </protein> in <cell_type> human peripheral blood mononuclear cells </cell_type> : variations during the menstrual cycle ."
  },
  {
    "input_text": "We have previously reported that human peripheral blood mononuclear cells ( PBMC ) contain type II estrogen binding sites ( type II EBS ) .",
    "target_text": "We have previously reported that <cell_type> human peripheral blood mononuclear cells </cell_type> ( <cell_type> PBMC </cell_type> ) contain type <protein> II estrogen binding sites </protein> ( <protein> type II EBS </protein> ) ."
  },
  {
    "input_text": "In this study , the fluctuations of type II EBS during the menstrual cycle were analyzed in 6 normally menstruating women .",
    "target_text": "In this study , the fluctuations of <protein> type II EBS </protein> during the menstrual cycle were analyzed in 6 normally menstruating women ."
  },
  {
    "input_text": "Approximately 3 times higher levels of type II EBS were found in the periovulatory period with respect to both follicular and luteal phases .",
    "target_text": "Approximately 3 times higher levels of <protein> type II EBS </protein> were found in the periovulatory period with respect to both follicular and luteal phases ."
  },
  {
    "input_text": "In postmenopausal women the mean type II EBS levels were similar to those observed in the follicular phase of the cycle .",
    "target_text": "In postmenopausal women the mean <protein> type II EBS </protein> levels were similar to those observed in the follicular phase of the cycle ."
  },
  {
    "input_text": "However , in 3 postmenopausal patients a short course of estrogen or tamoxifen resulted in a marked increase of type II EBS levels .",
    "target_text": "However , in 3 postmenopausal patients a short course of estrogen or tamoxifen resulted in a marked increase of <protein> type II EBS </protein> levels ."
  },
  {
    "input_text": "Tamoxifen was also found to compete with 17 beta-estradiol for type II EBS in PBMC , although to a lesser extent than diethylstilbestrol .",
    "target_text": "Tamoxifen was also found to compete with 17 beta-estradiol for <protein> type II EBS </protein> in <cell_type> PBMC </cell_type> , although to a lesser extent than diethylstilbestrol ."
  },
  {
    "input_text": "Mononuclear leukocyte glucocorticoid receptor binding characteristics and down-regulation in major depression .",
    "target_text": "<cell_type> Mononuclear leukocyte </cell_type> <protein> glucocorticoid receptor </protein> binding characteristics and down-regulation in major depression ."
  },
  {
    "input_text": "Some patients with major depressive disorder ( MDD ) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone ( DEX ) , yet they do not have Cushingoid features .",
    "target_text": "Some patients with major depressive disorder ( MDD ) have elevated plasma cortisol concentrations and show failure to suppress cortisol secretion upon administration of dexamethasone ( DEX ) , yet they do not have Cushingoid features ."
  },
  {
    "input_text": "To study whether this represents glucocorticoid ( GC ) resistance , [3H]-DEX-binding assays were used to measure , in vitro , the GC receptor affinity ( 1/Kd ) and number ( Bmax ) in mononuclear leukocytes of 11 MDD patients and 15 control subjects .",
    "target_text": "To study whether this represents glucocorticoid ( GC ) resistance , [3H]-DEX-binding assays were used to measure , in vitro , the <protein> GC receptor </protein> affinity ( 1/Kd ) and number ( Bmax ) in <cell_type> mononuclear leukocytes </cell_type> of 11 MDD patients and 15 control subjects ."
  },
  {
    "input_text": "No receptor abnormalities were detected in the MDD group ; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients , if present , probably lies beyond the initial receptor binding .",
    "target_text": "No receptor abnormalities were detected in the MDD group ; thus any cellular defect leading to a lack of responsiveness to GC in the MDD patients , if present , probably lies beyond the initial receptor binding ."
  },
  {
    "input_text": "DEX ( 1.0 mg orally ) was administered to study in vivo GC receptor down-regulation .",
    "target_text": "DEX ( 1.0 mg orally ) was administered to study in <protein> vivo GC receptor </protein> down-regulation ."
  },
  {
    "input_text": "Compared to the control group , fewer depressed subjects down-regulated Bmax after DEX .",
    "target_text": "Compared to the control group , fewer depressed subjects down-regulated Bmax after DEX ."
  },
  {
    "input_text": "By paired t-test , Bmax decreased significantly in the control group but not in the depressed group .",
    "target_text": "By paired t-test , Bmax decreased significantly in the control group but not in the depressed group ."
  },
  {
    "input_text": "Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation , severity of depression or cortisol concentrations across all the subjects .",
    "target_text": "Receptor number on the control day did not correlate significantly with the degree of receptor down-regulation , severity of depression or cortisol concentrations across all the subjects ."
  },
  {
    "input_text": "These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality , and they emphasize the importance of considering receptor studies in the context of GC -mediated cell processes in order to identify the exact cellular defect ( s ) leading to GC resistance .",
    "target_text": "These results do not lend support to previous reports suggesting that GC resistance in MDD results from a GC receptor-binding abnormality , and they emphasize the importance of considering receptor studies in the context of GC -mediated cell processes in order to identify the exact cellular defect ( s ) leading to GC resistance ."
  },
  {
    "input_text": "Ras-related GTP-binding proteins and leukocyte signal transduction .",
    "target_text": "<protein> Ras-related GTP-binding proteins </protein> and <cell_type> leukocyte </cell_type> signal transduction ."
  },
  {
    "input_text": "Many aspects of leukocyte function are regulated by both heterotrimeric and Ras-related GTP-binding proteins , but there is little definite information about their roles in the specialized processes utilized by leukocytes for cell killing .",
    "target_text": "Many aspects of <cell_type> leukocyte </cell_type> function are regulated by both <protein> heterotrimeric </protein> and <protein> Ras-related GTP-binding proteins </protein> , but there is little definite information about their roles in the specialized processes utilized by <cell_type> leukocytes </cell_type> for cell killing ."
  },
  {
    "input_text": "Recent progress in understanding the regulation of the phagocyte NADPH oxidase by the Rac GTP-binding proteins provides a basis for defining the operational characteristics of one such phagocyte system .",
    "target_text": "Recent progress in understanding the regulation of the <protein> phagocyte NADPH oxidase </protein> by the <protein> Rac GTP-binding proteins </protein> provides a basis for defining the operational characteristics of one such phagocyte system ."
  },
  {
    "input_text": "It is clear from various studies that the activity of the NADPH oxidase can be modulated through the regulation of the GTP-GDP state of Rac .",
    "target_text": "It is clear from various studies that the activity of the <protein> NADPH oxidase </protein> can be modulated through the regulation of the <protein> GTP-GDP state </protein> of <protein> Rac </protein> ."
  },
  {
    "input_text": "Proteins exist in leukocytes able to modify GTP-binding protein function in this manner , and their activity may be regulated by signals generated on phagocyte stimulation .",
    "target_text": "Proteins exist in <cell_type> leukocytes </cell_type> able to modify <protein> GTP-binding protein </protein> function in this manner , and their activity may be regulated by signals generated on phagocyte stimulation ."
  },
  {
    "input_text": "Proteins of the Ras superfamily are likely to be involved in a variety of normal phagocyte functions through their ability to modulate the assembly of actin filaments , direct vesicle trafficking and fusion , and so forth .",
    "target_text": "Proteins of the <protein> Ras superfamily </protein> are likely to be involved in a variety of normal phagocyte functions through their ability to modulate the assembly of <protein> actin filaments </protein> , direct vesicle trafficking and fusion , and so forth ."
  },
  {
    "input_text": "BSAP : a key regulator of B-cell development and differentiation .",
    "target_text": "<protein> BSAP </protein> : a key regulator of <cell_type> B-cell </cell_type> development and differentiation ."
  },
  {
    "input_text": "B-cell-specific activator protein ( BSAP ) is a recently identified member of the Pax-gene family of transcription factors ; in the lymphoid system , BSAP is produced only in B cells .",
    "target_text": "<protein> B-cell-specific activator protein </protein> ( <protein> BSAP </protein> ) is a recently identified member of the <DNA> Pax-gene family </DNA> of <protein> transcription factors </protein> ; in the lymphoid system , <protein> BSAP </protein> is produced only in <cell_type> B cells </cell_type> ."
  },
  {
    "input_text": "Here , Markus Neurath , Eckhard Stuber and Warren Strober describe the molecular structure of BSAP and focus on the ability of this protein to regulate the expression of B-cell-specific genes .",
    "target_text": "Here , Markus Neurath , Eckhard Stuber and Warren Strober describe the molecular structure of <protein> BSAP </protein> and focus on the ability of this protein to regulate the expression of <DNA> B-cell-specific genes </DNA> ."
  },
  {
    "input_text": "They propose that BSAP is a key protein of B cells and that it not only influence B-cell development but also influences the balance between B-cell proliferation and immunoglobulin secretion at later stages of B-cell differentiation .",
    "target_text": "They propose that <protein> BSAP </protein> is a <protein> key protein </protein> of <cell_type> B cells </cell_type> and that it not only influence B-cell development but also influences the balance between B-cell proliferation and <protein> immunoglobulin </protein> secretion at later stages of B-cell differentiation ."
  },
  {
    "input_text": "Down-regulation of NF-kappa B protein levels in activated human lymphocytes by 1,25-dihydroxyvitamin D3 [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jan 9 ; 93 ( 1 ) : 524 ]",
    "target_text": "Down-regulation of <protein> NF-kappa B protein </protein> levels in activated human lymphocytes by 1,25-dihydroxyvitamin D3 [ published erratum appears in Proc Natl Acad Sci U S A 1996 Jan 9 ; 93 ( 1 ) : 524 ]"
  },
  {
    "input_text": "The effect of 1,25-dihydroxyvitamin D3 [ 1,25(OH)2)D3 ] , a steroid hormone with immunomodulating properties , on nuclear factor kappa B ( NF-kappa B ) proteins was examined in in vitro activated normal human lymphocytes by Western blot analysis .",
    "target_text": "The effect of 1,25-dihydroxyvitamin D3 [ 1,25(OH)2)D3 ] , a steroid hormone with immunomodulating properties , on <protein> nuclear factor kappa B </protein> ( <protein> NF-kappa B </protein> ) proteins was examined in <cell_line> in vitro activated normal <cell_type> human lymphocytes </cell_type> </cell_line> by Western blot analysis ."
  },
  {
    "input_text": "Over a 72-hr period of activation , the expression of the 50-kDa NF-kappa B , p50 , and its precursor , p105 , was increased progressively .",
    "target_text": "Over a 72-hr period of activation , the expression of the <protein> 50-kDa NF-kappa B </protein> , <protein> p50 </protein> , and its precursor , <protein> p105 </protein> , was increased progressively ."
  },
  {
    "input_text": "When cells were activated in the presence of 1,25(OH)2D3 , the levels of the mature protein as well as its precursor were decreased .",
    "target_text": "When cells were activated in the presence of 1,25(OH)2D3 , the levels of the mature protein as well as its precursor were decreased ."
  },
  {
    "input_text": "The effect of the hormone on the levels of p50 was demonstrable in the cytosolic and nuclear compartments ; it required between 4 and 8 hr and was specific , as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were ineffective .",
    "target_text": "The effect of the hormone on the levels of <protein> p50 </protein> was demonstrable in the cytosolic and nuclear compartments ; it required between 4 and 8 hr and was specific , as 25-hydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were ineffective ."
  },
  {
    "input_text": "Besides p50 , 1,25(OH)2D3 decreased the levels of another NF-kappa B protein , namely c-rel .",
    "target_text": "Besides <protein> p50 </protein> , 1,25(OH)2D3 decreased the levels of another <protein> NF-kappa B protein </protein> , namely <protein> c-rel </protein> ."
  },
  {
    "input_text": "In addition , 1,25(OH)2D3 decreased the abundance of a specific DNA-protein complex formed upon incubation of nuclear extracts from activated lymphocytes with a labeled NF-kappa B DNA binding motif .",
    "target_text": "In addition , 1,25(OH)2D3 decreased the abundance of a <protein> specific DNA-protein complex </protein> formed upon incubation of nuclear extracts from activated lymphocytes with a labeled <protein> <protein> NF-kappa B </protein> DNA binding motif </protein> ."
  },
  {
    "input_text": "Further , 1,25(OH)2D3 inhibited the transcriptional activity of NF-kappa B in Jurkat cells transiently transfected with a construct containing four tandem repeats of the NF-kappa B binding sequence of the immunoglobulin kappa light chain gene linked to the chloramphenicol acetyltransferase reporter gene .",
    "target_text": "Further , 1,25(OH)2D3 inhibited the transcriptional activity of <protein> NF-kappa B </protein> in <cell_line> Jurkat cells </cell_line> transiently transfected with a <DNA> construct </DNA> containing four <DNA> tandem repeats </DNA> of the <DNA> <protein> NF-kappa B </protein> binding sequence </DNA> of the <DNA> immunoglobulin kappa light chain gene </DNA> linked to the <DNA> <protein> chloramphenicol acetyltransferase </protein> reporter gene </DNA> ."
  },
  {
    "input_text": "These observations demonstrate directly that there is de novo synthesis of NF-kappa B during human lymphocyte activation and suggest that this process is hormonally regulated .",
    "target_text": "These observations demonstrate directly that there is de novo synthesis of <protein> NF-kappa B </protein> during human lymphocyte activation and suggest that this process is hormonally regulated ."
  },
  {
    "input_text": "The myeloid zinc finger gene , MZF-1 , regulates the CD34 promoter in vitro .",
    "target_text": "The <DNA> myeloid zinc finger gene </DNA> , <DNA> MZF-1 </DNA> , regulates the <DNA> CD34 promoter </DNA> in vitro ."
  },
  {
    "input_text": "MZF-1 is a C2H2 zinc finger gene encoding a putative transcriptional regulator of myeloid differentiation .",
    "target_text": "<DNA> MZF-1 </DNA> is a <DNA> C2H2 zinc finger gene </DNA> encoding a <protein> putative transcriptional regulator </protein> of myeloid differentiation ."
  },
  {
    "input_text": "The MZF-1 protein contains 13 C2H2 zinc fingers arranged in bipartite DNA binding domains containing zinc fingers through 4 and , in the carboxy-terminus , 5 through 13 .",
    "target_text": "The <DNA> MZF-1 </DNA> protein contains 13 <protein> C2H2 zinc fingers </protein> arranged in bipartite <protein> DNA binding domains </protein> containing <protein> zinc fingers </protein> through 4 and , in the <protein> carboxy-terminus </protein> , 5 through 13 ."
  },
  {
    "input_text": "We previously identified the DNA consensus binding site recognized by the two DNA binding domains .",
    "target_text": "We previously identified the <DNA> DNA consensus binding site </DNA> recognized by the two <protein> DNA binding domains </protein> ."
  },
  {
    "input_text": "To assess the transcription regulatory function of MZF-1 , the full-length MZF-1 coding region was fused to the DNA binding domain of the yeast transactivator GAL4 .",
    "target_text": "To assess the transcription regulatory function of <DNA> MZF-1 </DNA> , the full-length <DNA> MZF-1 </DNA> coding region was fused to the <protein> DNA binding domain </protein> of the <protein> yeast transactivator <protein> GAL4 </protein> </protein> ."
  },
  {
    "input_text": "The expression vector was cotransfected with the chloramphenicol acetyl transferase ( CAT ) reporter gene regulated by the thymidine kinase promoter containing GAL4 DNA binding sites into NIH 3T3 , 293 , K562 , and Jurkat cell lines .",
    "target_text": "The expression vector was cotransfected with the <DNA> <protein> chloramphenicol acetyl transferase </protein> ( CAT ) reporter gene </DNA> regulated by the <DNA> <protein> thymidine kinase </protein> promoter </DNA> containing <DNA> <protein> GAL4 </protein> DNA binding sites </DNA> into <cell_line> NIH 3T3 </cell_line> , <cell_line> 293 </cell_line> , <cell_line> K562 </cell_line> , and <cell_line> Jurkat cell lines </cell_line> ."
  },
  {
    "input_text": "MZF-1 represses CAT reporter gene expression via GAL4 binding sites in the nonhematopoietic cell lines NIH 3T3 and 293 .",
    "target_text": "<DNA> MZF-1 </DNA> represses <DNA> CAT reporter gene </DNA> expression via <protein> GAL4 </protein> binding sites in the <cell_line> nonhematopoietic cell lines </cell_line> <cell_line> NIH 3T3 </cell_line> and <cell_line> 293 </cell_line> ."
  },
  {
    "input_text": "In contrast , MZF-1 activates CAT reporter gene expression in the hematopoietic cell lines K562 and Jurkat .",
    "target_text": "In contrast , <DNA> MZF-1 </DNA> activates <DNA> CAT reporter gene </DNA> expression in the <cell_line> hematopoietic cell lines </cell_line> <cell_line> K562 </cell_line> and <cell_line> Jurkat </cell_line> ."
  },
  {
    "input_text": "The MZF-1 binding sites are present in the promoters of several genes expressed during myeloid differentiation , including the CD34 promoter .",
    "target_text": "The <DNA> <DNA> MZF-1 </DNA> binding sites </DNA> are present in the <DNA> promoters </DNA> of several <DNA> genes </DNA> expressed during myeloid differentiation , including the <DNA> CD34 promoter </DNA> ."
  },
  {
    "input_text": "MZF-1 transcriptional regulation of this physiologically relevant promoter was assessed in both hematopoietic and nonhematopoietic cell lines .",
    "target_text": "<DNA> MZF-1 </DNA> transcriptional regulation of this <DNA> physiologically relevant promoter </DNA> was assessed in both <cell_line> hematopoietic </cell_line> and <cell_line> nonhematopoietic cell lines </cell_line> ."
  },
  {
    "input_text": "Recombinant MZF-1 protein specifically binds to the consensus binding sites in the CD34 promoter in mobility shift assays .",
    "target_text": "<protein> Recombinant <DNA> MZF-1 </DNA> protein </protein> specifically binds to the <DNA> consensus binding sites </DNA> in the <DNA> CD34 promoter </DNA> in mobility shift assays ."
  },
  {
    "input_text": "MZF-1 expression vectors were cotransfected with the luciferase reporter plasmids regulated by the CD34 promoter into both nonhematopoietic and hematopoietic cell lines .",
    "target_text": "<DNA> MZF-1 </DNA> expression vectors were cotransfected with the <DNA> luciferase reporter plasmids </DNA> regulated by the <DNA> CD34 promoter </DNA> into both nonhematopoietic and hematopoietic cell lines ."
  },
  {
    "input_text": "As with the heterologous DNA binding domain , MZF-1 represses reporter gene expression in nonhematopoietic cell lines and activates expression in hematopoietic cell lines .",
    "target_text": "As with the heterologous <protein> DNA binding domain </protein> , <DNA> MZF-1 </DNA> represses <DNA> reporter gene </DNA> expression in <cell_line> nonhematopoietic cell lines </cell_line> and activates expression in <cell_line> hematopoietic cell lines </cell_line> ."
  },
  {
    "input_text": "Activation of CD34 expression in hematopoietic cell lines is dependent on the presence of intact MZF-1 binding sites .",
    "target_text": "Activation of <protein> CD34 </protein> expression in <cell_line> hematopoietic cell lines </cell_line> is dependent on the presence of intact <DNA> <DNA> MZF-1 </DNA> binding sites </DNA> ."
  },
  {
    "input_text": "The cell type-specific regulation of the CD34 promoter by MZF-1 suggests the presence of tissue-specific regulators/adapters or differential MZF-1 modifications that determine MZF-1 transcriptional regulatory function .",
    "target_text": "The cell type-specific regulation of the <DNA> CD34 promoter </DNA> by <DNA> MZF-1 </DNA> suggests the presence of tissue-specific regulators/adapters or differential <DNA> MZF-1 </DNA> modifications that determine <DNA> MZF-1 </DNA> transcriptional regulatory function ."
  },
  {
    "input_text": "The murine BCL6 gene is induced in activated lymphocytes as an immediate early gene .",
    "target_text": "The murine <DNA> BCL6 gene </DNA> is induced in <cell_type> activated lymphocytes </cell_type> as an <DNA> immediate early gene </DNA> ."
  },
  {
    "input_text": "The chromosomal translocation involving 3q27 is often detected in human B-cell lymphomas , especially diffuse lymphomas with a large-cell component .",
    "target_text": "The chromosomal translocation involving <DNA> 3q27 </DNA> is often detected in <cell_type> human B-cell lymphomas </cell_type> , especially diffuse lymphomas with a large-cell component ."
  },
  {
    "input_text": "The BCL6 gene has been isolated from the chromosomal breakpoint in these lymphomas .",
    "target_text": "The <DNA> BCL6 gene </DNA> has been isolated from the chromosomal breakpoint in these lymphomas ."
  },
  {
    "input_text": "Here we cloned the murine BCL6 ( mBCL6 ) cDNA from the muscle cDNA library using the human BCL6 ( hBCL6 ) cDNA as a probe .",
    "target_text": "Here we cloned the <DNA> <protein> murine BCL6 </protein> ( mBCL6 ) cDNA </DNA> from the <DNA> muscle cDNA library </DNA> using the <DNA> <protein> human BCL6 </protein> ( hBCL6 ) cDNA </DNA> as a probe ."
  },
  {
    "input_text": "The predicted amino acid sequence was 95 % identical to that of hBCL6 .",
    "target_text": "The predicted amino acid sequence was 95 % identical to that of <protein> hBCL6 </protein> ."
  },
  {
    "input_text": "It contains six repeats of the Kruppel-like zinc-finger motif that are completely identical to those of hBCL6 , indicating that the BCL6 gene is well conserved between humans and mice .",
    "target_text": "It contains six repeats of the <protein> Kruppel-like zinc-finger motif </protein> that are completely identical to those of <protein> hBCL6 </protein> , indicating that the <DNA> BCL6 gene </DNA> is well conserved between humans and mice ."
  },
  {
    "input_text": "Expression of the mBCL6 gene was ubiquitously detected in adult mouse tissues including lymphatic organs .",
    "target_text": "Expression of the <DNA> mBCL6 gene </DNA> was ubiquitously detected in adult mouse tissues including lymphatic organs ."
  },
  {
    "input_text": "Furthermore , it was induced in lymphocytes activated with phorbol ester and Ca2+ ionophore within 30 min after stimulation .",
    "target_text": "Furthermore , it was induced in <cell_type> lymphocytes </cell_type> activated with phorbol ester and Ca2+ ionophore within 30 min after stimulation ."
  },
  {
    "input_text": "This induction was not inhibited by treatment of the cells with a protein synthesis inhibitor , cycloheximide .",
    "target_text": "This induction was not inhibited by treatment of the cells with a protein synthesis inhibitor , cycloheximide ."
  },
  {
    "input_text": "These results suggest that BCL6 plays a role in activated lymphocytes as an immediate early gene .",
    "target_text": "These results suggest that <protein> BCL6 </protein> plays a role in <cell_type> activated <cell_type> lymphocytes </cell_type> </cell_type> as an immediate early gene ."
  },
  {
    "input_text": "The role of BSAP ( Pax-5 ) in B-cell development .",
    "target_text": "The role of <protein> BSAP </protein> ( <protein> Pax-5 </protein> ) in B-cell development ."
  },
  {
    "input_text": "The hierarchy of transcriptional control in B-cell development has recently been analyzed by targeted gene inactivation in the mouse .",
    "target_text": "The hierarchy of transcriptional control in B-cell development has recently been analyzed by targeted gene inactivation in the mouse ."
  },
  {
    "input_text": "In this manner , the paired box containing gene Pax-5 , encoding the B cell specific transcription factor BSAP , has been shown to play a key role in early B lymphopoiesis .",
    "target_text": "In this manner , the <DNA> paired box containing gene </DNA> <DNA> Pax-5 </DNA> , encoding the <protein> B cell specific transcription factor </protein> <protein> BSAP </protein> , has been shown to play a key role in early B lymphopoiesis ."
  },
  {
    "input_text": "Other experimental strategies have implicated BSAP in the control of cell proliferation , isotype switching and transcription of the immunoglobulin heavy-chain gene at late stages of B-cell differentiation .",
    "target_text": "Other experimental strategies have implicated <protein> BSAP </protein> in the control of cell proliferation , isotype switching and transcription of the <DNA> <protein> immunoglobulin heavy-chain </protein> gene </DNA> at late stages of B-cell differentiation ."
  },
  {
    "input_text": "The DNA-binding properties of two heat shock factors , HSF1 and HSF3 , are induced in the avian erythroblast cell line HD6 .",
    "target_text": "The DNA-binding properties of <protein> two heat shock factors </protein> , <protein> HSF1 </protein> and <protein> HSF3 </protein> , are induced in the <cell_line> avian erythroblast cell line </cell_line> <cell_line> HD6 </cell_line> ."
  },
  {
    "input_text": "Avian cells express three heat shock transcription factor ( HSF ) genes corresponding to a novel factor , HSF3 , and homologs of mouse and human HSF1 and HSF2 .",
    "target_text": "Avian cells express three <DNA> <protein> heat shock transcription factor </protein> ( <protein> HSF </protein> ) genes </DNA> corresponding to a <protein> novel factor </protein> , <protein> HSF3 </protein> , and homologs of mouse and human <protein> HSF1 </protein> and <protein> HSF2 </protein> ."
  },
  {
    "input_text": "Analysis of the biochemical and cell biological properties of these HSFs reveals that HSF3 has properties in common with both HSF1 and HSF2 and yet has features which are distinct from both .",
    "target_text": "Analysis of the biochemical and cell biological properties of these <protein> HSFs </protein> reveals that <protein> HSF3 </protein> has properties in common with both <protein> HSF1 </protein> and <protein> HSF2 </protein> and yet has features which are distinct from both ."
  },
  {
    "input_text": "HSF3 is constitutively expressed in the erythroblast cell line HD6 , the lymphoblast cell line MSB , and embryo fibroblasts , and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock .",
    "target_text": "<protein> HSF3 </protein> is constitutively expressed in the <cell_line> erythroblast cell line HD6 </cell_line> , the <cell_line> lymphoblast cell line MSB </cell_line> , and <cell_line> embryo fibroblasts </cell_line> , and yet its DNA-binding activity is induced only upon exposure of HD6 cells to heat shock ."
  },
  {
    "input_text": "Acquisition of HSF3 DNA-binding activity in HD6 cells is accompanied by oligomerization from a non-DNA-binding dimer to a DNA-binding trimer , whereas the effect of heat shock on HSF1 is oligomerization of an inert monomer to a DNA-binding trimer .",
    "target_text": "Acquisition of <protein> HSF3 </protein> DNA-binding activity in <cell_line> HD6 cells </cell_line> is accompanied by oligomerization from a <protein> non-DNA-binding dimer </protein> to a <protein> DNA-binding trimer </protein> , whereas the effect of heat shock on <protein> HSF1 </protein> is oligomerization of an <protein> inert monomer </protein> to a <protein> DNA-binding trimer </protein> ."
  },
  {
    "input_text": "Induction of HSF3 DNA-binding activity is delayed compared with that of HSF1 .",
    "target_text": "Induction of <protein> HSF3 </protein> DNA-binding activity is delayed compared with that of <protein> HSF1 </protein> ."
  },
  {
    "input_text": "As occurs for HSF1 , heat shock leads to the translocation of HSF3 to the nucleus .",
    "target_text": "As occurs for <protein> HSF1 </protein> , heat shock leads to the translocation of <protein> HSF3 </protein> to the nucleus ."
  },
  {
    "input_text": "HSF exhibits the properties of a transcriptional activator , as judged from the stimulatory activity of transiently overexpressed HSF3 measured by using a heat shock element-containing reporter construct and as independently assayed by the activity of a chimeric GAL4 -HSF3 protein on a GAL4 reporter construct .",
    "target_text": "HSF exhibits the properties of a <protein> transcriptional activator </protein> , as judged from the stimulatory activity of <protein> transiently overexpressed <protein> HSF3 </protein> </protein> measured by using a <DNA> heat shock element-containing reporter construct </DNA> and as independently assayed by the activity of a <protein> chimeric <protein> GAL4 </protein> <protein> -HSF3 </protein> protein </protein> on a <DNA> <protein> GAL4 </protein> reporter construct </DNA> ."
  },
  {
    "input_text": "These results reveal that HSF3 is negatively regulated in avian cells and acquires DNA-binding activity in certain cells upon heat shock .",
    "target_text": "These results reveal that <protein> HSF3 </protein> is negatively regulated in <cell_type> avian cells </cell_type> and acquires DNA-binding activity in certain cells upon heat shock ."
  },
  {
    "input_text": "Direct demonstration of NFATp dephosphorylation and nuclear localization in activated HT-2 cells using a specific NFATp polyclonal antibody .",
    "target_text": "Direct demonstration of <protein> NFATp </protein> dephosphorylation and nuclear localization in <cell_line> activated <cell_line> HT-2 cells </cell_line> </cell_line> using a specific <protein> <protein> NFATp </protein> polyclonal antibody </protein> ."
  },
  {
    "input_text": "Nuclear factor of activated T cells ( NFAT ) regulates transcription of a number of cytokine genes , and NFAT DNA binding activity is stimulated following T cell activation .",
    "target_text": "<protein> Nuclear factor of activated T cells </protein> ( <protein> NFAT </protein> ) regulates transcription of a number of <protein> cytokine genes </protein> , and <protein> NFAT </protein> DNA binding activity is stimulated following T cell activation ."
  },
  {
    "input_text": "Several lines of evidence have suggested that NFAT is a substrate for calcineurin , a serine/threonine phosphatase .",
    "target_text": "Several lines of evidence have suggested that <protein> NFAT </protein> is a substrate for <protein> calcineurin </protein> , a <protein> serine/threonine phosphatase </protein> ."
  },
  {
    "input_text": "Using a polyclonal antibody to murine NFATp , Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa NFATp protein was highly expressed in thymus and spleen .",
    "target_text": "Using a polyclonal antibody to <protein> murine <protein> NFATp </protein> </protein> , Western blot analysis of various mouse tissues demonstrated that the 110-130-kDa <protein> <protein> NFATp </protein> protein </protein> was highly expressed in thymus and spleen ."
  },
  {
    "input_text": "Treatment of immunoprecipitated NFATp from untreated HT-2 cells with calcineurin resulted in the dephosphorylation of NFATp , demonstrating that NFATp is an in vitro substrate for calcineurin .",
    "target_text": "Treatment of immunoprecipitated <protein> NFATp </protein> from untreated <cell_line> HT-2 cells </cell_line> with <protein> calcineurin </protein> resulted in the dephosphorylation of <protein> NFATp </protein> , demonstrating that <protein> NFATp </protein> is an in vitro substrate for <protein> calcineurin </protein> ."
  },
  {
    "input_text": "NFATp immunoprecipitated from 32P-labeled HT-2 cells migrated as an approximately 120-kDa protein that was localized to the cytosol of the cells .",
    "target_text": "<protein> NFATp </protein> immunoprecipitated from <cell_line> 32P-labeled <cell_line> HT-2 cells </cell_line> </cell_line> migrated as an approximately 120-kDa protein that was localized to the cytosol of the cells ."
  },
  {
    "input_text": "Treatment of the cells with ionomycin resulted in a decrease in the molecular weight of NFATp and a loss of 32P , consistent with NFATp dephosphorylation .",
    "target_text": "Treatment of the cells with ionomycin resulted in a decrease in the molecular weight of <protein> NFATp </protein> and a loss of 32P , consistent with <protein> NFATp </protein> dephosphorylation ."
  },
  {
    "input_text": "The dephosphorylation of NFATp was accompanied by localization of the protein to the nuclear fraction .",
    "target_text": "The dephosphorylation of <protein> NFATp </protein> was accompanied by localization of the protein to the nuclear fraction ."
  },
  {
    "input_text": "Both of these events were blocked by preincubation of the cells with FK506 , a calcineurin inhibitor , consistent with the hypothesis that NFATp is a calcineurin substrate in cells .",
    "target_text": "Both of these events were blocked by preincubation of the cells with FK506 , a <protein> calcineurin </protein> inhibitor , consistent with the hypothesis that <protein> NFATp </protein> is a <protein> calcineurin </protein> substrate in cells ."
  },
  {
    "input_text": "Activation and expression of the nuclear factors of activated T cells , NFATp and NFATc , in human natural killer cells : regulation upon CD16 ligand binding .",
    "target_text": "Activation and expression of the <protein> nuclear factors </protein> of <cell_type> activated T cells </cell_type> , <protein> NFATp </protein> and <protein> NFATc </protein> , in <cell_type> human natural killer cells </cell_type> : regulation upon <protein> CD16 </protein> ligand binding ."
  },
  {
    "input_text": "The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer ( NK ) cells have not been elucidated .",
    "target_text": "The putative factors that couple the signal transduction from surface receptors to the activation of <protein> cytokine </protein> synthesis in <cell_type> natural killer ( NK ) cells </cell_type> have not been elucidated ."
  },
  {
    "input_text": "We report here that the nuclear factor of activated T cells ( NFATp ) , a cyclosporin A ( CsA ) -sensitive factor that regulates the transcription of several cytokines , mediates CD16 -induced activation of cytokine genes in human NK cells .",
    "target_text": "We report here that the <protein> nuclear factor </protein> of <cell_type> activated T cells </cell_type> ( <protein> NFATp </protein> ) , a <protein> cyclosporin A ( CsA ) -sensitive factor </protein> that regulates the transcription of several <protein> cytokines </protein> , mediates <protein> CD16 </protein> -induced activation of <protein> cytokine genes </protein> in <cell_type> human NK cells </cell_type> ."
  },
  {
    "input_text": "CD16 ( Fc gamma RIIIA ) -induced expression of cytokine mRNA in NK cells occurs via a CsA -sensitive and Ca(2+)-dependent mechanism .",
    "target_text": "<protein> CD16 </protein> ( <protein> Fc gamma RIIIA </protein> ) -induced expression of <RNA> cytokine mRNA </RNA> in <cell_type> NK cells </cell_type> occurs via a CsA -sensitive and Ca(2+)-dependent mechanism ."
  },
  {
    "input_text": "Stimulation of NK cells with CD16 ligands induces NFAT -like DNA binding activity in the nuclear extracts from these cells , as detected in electrophoretic mobility shift assays .",
    "target_text": "Stimulation of <cell_type> NK cells </cell_type> with <protein> CD16 </protein> ligands induces <protein> NFAT </protein> -like DNA binding activity in the nuclear extracts from these cells , as detected in electrophoretic mobility shift assays ."
  },
  {
    "input_text": "This occurs with fast kinetics after stimulation , via a CsA -sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis .",
    "target_text": "This occurs with fast kinetics after stimulation , via a CsA -sensitive and Ca(2+)-dependent mechanism that does not require de novo protein synthesis ."
  },
  {
    "input_text": "NK cell NFAT is present in the cytosol of nonstimulated cells , migrates to the nucleus upon stimulation , and can associate with AP-1 .",
    "target_text": "<protein> NK cell NFAT </protein> is present in the cytosol of <cell_type> nonstimulated cells </cell_type> , migrates to the nucleus upon stimulation , and can associate with <protein> AP-1 </protein> ."
  },
  {
    "input_text": "Two distinct molecules , NFATp and NFATc , have been reported to mediate NFAT activity .",
    "target_text": "Two distinct molecules , <protein> NFATp </protein> and <protein> NFATc </protein> , have been reported to mediate <protein> NFAT </protein> activity ."
  },
  {
    "input_text": "The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily , if not exclusively , NFATp , and Western blot analysis shows that this has the same electrophoretic mobility ( approximately 120 kD ) as that of T lymphocytes .",
    "target_text": "The results of supershift assays using NFATp- and NFATc- specific antibodies indicate that NK cell activation early after <protein> CD16 </protein> ligand binding involves primarily , if not exclusively , <protein> NFATp </protein> , and Western blot analysis shows that this has the same electrophoretic mobility ( approximately 120 kD ) as that of <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "NK cells do not express NFATc constitutively , but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands .",
    "target_text": "<cell_type> NK cells </cell_type> do not express <protein> NFATc </protein> constitutively , but <RNA> <protein> NFATc </protein> mRNA </RNA> accumulation is induced in these cells within 2 h of stimulation with CD16 ligands ."
  },
  {
    "input_text": "However , supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester -stimulated cells at any time tested , up to 4 h .",
    "target_text": "However , supershift assays using the available <protein> mAb </protein> recognizing the <protein> T cell <protein> NFATc </protein> </protein> revealed no detectable <protein> NFATc </protein> protein in nuclear and cytoplasmic extracts from CD16- or <cell_line> phorbol ester -stimulated cells </cell_line> at any time tested , up to 4 h ."
  },
  {
    "input_text": "These results provide the first direct evidence that both CsA -sensitive transcription factors , NFATp and NFATc , are expressed in human NK cells , and that their activation and/or expression can be regulated in primary cells by a single stimulus , that , in the case of CD16 in NK cells , results in early activation of NFATp and subsequently induced expression of NFATc mRNA .",
    "target_text": "These results provide the first direct evidence that both <protein> CsA -sensitive <protein> transcription factors </protein> </protein> , <protein> NFATp </protein> and <protein> NFATc </protein> , are expressed in human <cell_type> NK cells </cell_type> , and that their activation and/or expression can be regulated in primary cells by a single stimulus , that , in the case of CD16 in <cell_type> NK cells </cell_type> , results in early activation of <protein> NFATp </protein> and subsequently induced expression of <RNA> <protein> NFATc </protein> mRNA </RNA> ."
  },
  {
    "input_text": "Interleukin 2 signaling involves the phosphorylation of Stat proteins .",
    "target_text": "Interleukin 2 signaling involves the phosphorylation of <protein> Stat proteins </protein> ."
  },
  {
    "input_text": "One of the most important cytokines involved in immune response regulation is interleukin 2 ( IL-2 ) , a potent activator of the proliferation and function of T lymphocytes and natural killer cells .",
    "target_text": "One of the most important <protein> cytokines </protein> involved in immune response regulation is interleukin 2 ( IL-2 ) , a potent activator of the proliferation and function of <cell_type> T <cell_type> lymphocytes </cell_type> </cell_type> and <cell_type> natural killer cells </cell_type> ."
  },
  {
    "input_text": "The mechanisms by which the effects of IL-2 are propagated within cells are not understood .",
    "target_text": "The mechanisms by which the effects of <protein> IL-2 </protein> are propagated within cells are not understood ."
  },
  {
    "input_text": "While the binding of IL-2 to its receptor was recently shown to lead to the activation of two kinases , Jak-1 and Jak-3 , subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized .",
    "target_text": "While the binding of <protein> IL-2 </protein> to its receptor was recently shown to lead to the activation of two <protein> kinases </protein> , <protein> Jak-1 </protein> and <protein> Jak-3 </protein> , subsequent steps in the signaling pathway to the nucleus that lead to the activation of specific genes had not been characterized ."
  },
  {
    "input_text": "Since many cytokines that activate Jak kinases also lead to the tyrosine phosphorylation and activation of members of the Stat family of transcription factors , the ability of IL-2 to trigger Stat phosphorylation was examined .",
    "target_text": "Since many <protein> cytokines </protein> that activate <protein> Jak <protein> kinases </protein> </protein> also lead to the tyrosine phosphorylation and activation of members of the <protein> Stat family </protein> of <protein> transcription factors </protein> , the ability of <protein> IL-2 </protein> to trigger Stat phosphorylation was examined ."
  },
  {
    "input_text": "Exposure of activated human T lymphocytes or of a natural killer cell line ( NKL ) to IL-2 leads to the phosphorylation of Stat1 alpha , Stat1 beta , and Stat3 , as well as of two Stat-related proteins , p94 and p95 .",
    "target_text": "Exposure of activated <cell_type> human <cell_type> T lymphocytes </cell_type> </cell_type> or of a <cell_line> <cell_type> natural killer cell </cell_type> line </cell_line> ( <cell_line> NKL </cell_line> ) to <protein> IL-2 </protein> leads to the phosphorylation of <protein> Stat1 alpha </protein> , <protein> Stat1 beta </protein> , and <protein> Stat3 </protein> , as well as of two <protein> Stat-related proteins </protein> , <protein> p94 </protein> and <protein> p95 </protein> ."
  },
  {
    "input_text": "p94 and p95 share homology with Stat1 at the phosphorylation site and in the Src homology 2 ( SH2 ) domain , but otherwise are immunologically distinct from Stat1 .",
    "target_text": "<protein> p94 </protein> and <protein> p95 </protein> share homology with <protein> Stat1 </protein> at the <protein> phosphorylation site </protein> and in the <protein> Src homology 2 ( SH2 ) domain </protein> , but otherwise are immunologically distinct from <protein> Stat1 </protein> ."
  },
  {
    "input_text": "These Stat proteins were found to translocate to the nucleus and to bind to a specific DNA sequence .",
    "target_text": "These <protein> Stat proteins </protein> were found to translocate to the nucleus and to bind to a <DNA> specific DNA sequence </DNA> ."
  },
  {
    "input_text": "These findings suggest a mechanism by which IL-2 binding to its receptor may activate specific genes involved in immune cell function .",
    "target_text": "These findings suggest a mechanism by which <protein> IL-2 </protein> binding to its receptor may activate <DNA> specific genes </DNA> involved in immune cell function ."
  },
  {
    "input_text": "Expression of c-fos correlates with IFN-alpha responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia .",
    "target_text": "Expression of <DNA> c-fos </DNA> correlates with <protein> IFN-alpha </protein> responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia ."
  },
  {
    "input_text": "This study evaluates ( i ) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and ( ii ) their modulations subsequent to in vivo therapy with rIFN-alpha 2c .",
    "target_text": "This study evaluates ( i ) constitutive levels of <DNA> oncogene </DNA> and <RNA> p53 transcripts </RNA> in chronic phase CML patients and ( ii ) their modulations subsequent to in vivo therapy with <protein> rIFN-alpha 2c </protein> ."
  },
  {
    "input_text": "Peripheral blood mononuclear cells ( pbmc ) and bone marrow cells of 26 patients were examined for c-fos , c-myc , p53 and the hybrid bcr/abl mRNA levels .",
    "target_text": "<cell_type> Peripheral blood mononuclear cells </cell_type> ( <cell_type> pbmc </cell_type> ) and <cell_type> bone marrow cells </cell_type> of 26 patients were examined for c-fos , c-myc , p53 and the hybrid bcr/abl mRNA levels ."
  },
  {
    "input_text": "Results indicated that ( i ) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy ( p < 0.01 ) and positively correlated with the proportion of lymphocytes ( r = 0.6895 , p < 0.01 ) and negatively with the proportion of immature cells ( r = -0.568 , p < 0.01 ) contained in the pbmc preparations tested , ( ii ) constitutive mRNA levels of the hybrid bcr/abl , c-myc and p53 are positively correlated with each other , but failed to relate to disease parameters , and ( iii ) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc mRNA levels in responder patients .",
    "target_text": "Results indicated that ( i ) constitutive <RNA> c-fos transcript </RNA> levels are significantly higher in patients subsequently responding to <protein> IFN-alpha </protein> therapy ( p < 0.01 ) and positively correlated with the proportion of <cell_type> lymphocytes </cell_type> ( r = 0.6895 , p < 0.01 ) and negatively with the proportion of <cell_type> immature cells </cell_type> ( r = -0.568 , p < 0.01 ) contained in the <cell_type> pbmc </cell_type> preparations tested , ( ii ) <RNA> constitutive mRNA </RNA> levels of the <DNA> hybrid bcr/abl </DNA> , <DNA> c-myc </DNA> and <DNA> p53 </DNA> are positively correlated with each other , but failed to relate to disease parameters , and ( iii ) acute and chronic in vivo exposure to <protein> IFN-alpha </protein> is accompanied by upregulation of <DNA> c-fos </DNA> and downregulation of <RNA> c-myc mRNA </RNA> levels in responder patients ."
  },
  {
    "input_text": "Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes .",
    "target_text": "Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of <protein> estrogen receptors </protein> in <cell_type> human peripheral monocytes </cell_type> ."
  },
  {
    "input_text": "PROBLEM : The clinical significance of the differential expression of estrogen receptor ( ER ) in human monocytes was evaluated .",
    "target_text": "PROBLEM : The clinical significance of the differential expression of <protein> estrogen receptor </protein> ( <protein> ER </protein> ) in <cell_type> human monocytes </cell_type> was evaluated ."
  },
  {
    "input_text": "METHOD : Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy .",
    "target_text": "METHOD : Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy ."
  },
  {
    "input_text": "In addition , the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine .",
    "target_text": "In addition , the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine ."
  },
  {
    "input_text": "RESULTS : During menopause there is a significant decrease in the percentage of ER positive monocytes , and an increase in blood monocyte number , which declines following estrogen replacement therapy to values of the young .",
    "target_text": "RESULTS : During menopause there is a significant decrease in the percentage of <cell_type> <protein> ER </protein> positive monocytes </cell_type> , and an increase in <cell_type> blood <cell_type> monocyte </cell_type> </cell_type> number , which declines following estrogen replacement therapy to values of the young ."
  },
  {
    "input_text": "CONCLUSIONS : These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes .",
    "target_text": "CONCLUSIONS : These findings suggest that estrogen modulates the <cell_type> monocyte </cell_type> numbers and its effects may be mediated through the <protein> ER </protein> in the <cell_type> monocytes </cell_type> ."
  },
  {
    "input_text": "Staphylococcal enterotoxins modulate interleukin 2 receptor expression and ligand-induced tyrosine phosphorylation of the Janus protein- tyrosine kinase 3 ( Jak3 ) and signal transducers and activators of transcription ( Stat proteins ) .",
    "target_text": "<protein> Staphylococcal enterotoxins </protein> modulate <protein> interleukin 2 receptor </protein> expression and ligand-induced tyrosine phosphorylation of the <protein> Janus protein- tyrosine kinase 3 </protein> ( <protein> Jak3 </protein> ) and <protein> signal transducers and activators of transcription </protein> ( <protein> Stat proteins </protein> ) ."
  },
  {
    "input_text": "Staphylococcal enterotoxins ( SE ) stimulate T cells expressing the appropriate variable region beta chain of ( V beta ) T-cell receptors and have been implicated in the pathogenesis of several autoimmune diseases .",
    "target_text": "<protein> Staphylococcal enterotoxins </protein> ( <protein> SE </protein> ) stimulate <cell_type> T cells </cell_type> expressing the appropriate <protein> <protein> variable region beta chain </protein> of ( <protein> V beta </protein> ) T-cell receptors </protein> and have been implicated in the pathogenesis of several autoimmune diseases ."
  },
  {
    "input_text": "Depending on costimulatory signals , SE induce either proliferation or anergy in T cells .",
    "target_text": "Depending on costimulatory signals , <protein> SE </protein> induce either proliferation or anergy in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "In addition , SE can induce an interleukin-2 ( IL-2 ) nonresponsive state and apoptosis .",
    "target_text": "In addition , <protein> SE </protein> can induce an <protein> interleukin-2 </protein> ( <protein> IL-2 </protein> ) nonresponsive state and apoptosis ."
  },
  {
    "input_text": "Here , we show that SE induce dynamic changes in the expression of and signal transduction through the IL-2 receptor ( IL-2R ) beta and gamma chains ( IL-2R beta and IL-2R gamma ) in human antigen-specific CD4+ T-cell lines .",
    "target_text": "Here , we show that <protein> SE </protein> induce dynamic changes in the expression of and signal transduction through the IL-2 receptor ( IL-2R ) beta and gamma chains ( <protein> IL-2R beta </protein> and <protein> IL-2R gamma </protein> ) in <cell_line> human antigen-specific CD4+ T-cell lines </cell_line> ."
  },
  {
    "input_text": "Thus , after 4 hr of exposure to SEA and SEB , the expression of IL-2R beta was down-regulated , IL-2R gamma was slightly up-regulated , while IL-2R alpha remained largely unaffected .",
    "target_text": "Thus , after 4 hr of exposure to <protein> SEA </protein> and <protein> SEB </protein> , the expression of <protein> IL-2R beta </protein> was down-regulated , <protein> IL-2R gamma </protein> was slightly up-regulated , while <protein> IL-2R alpha </protein> remained largely unaffected ."
  },
  {
    "input_text": "The changes in the composition of IL-2Rs were accompanied by inhibition of IL-2 -induced tyrosine phosphorylation of the Janus protein- tyrosine kinase 3 ( Jak3 ) and signal transducers and activators of transcription called Stat3 and Stat5 .",
    "target_text": "The changes in the composition of <protein> IL-2Rs </protein> were accompanied by inhibition of <protein> IL-2 </protein> -induced tyrosine phosphorylation of the <protein> Janus protein- tyrosine kinase 3 </protein> ( <protein> Jak3 </protein> ) and <protein> signal transducers and activators of transcription </protein> called <protein> Stat3 </protein> and <protein> Stat5 </protein> ."
  },
  {
    "input_text": "In parallel experiments , IL-2 -driven proliferation was inhibited significantly .",
    "target_text": "In parallel experiments , <protein> IL-2 </protein> -driven proliferation was inhibited significantly ."
  },
  {
    "input_text": "After 16 hr of exposure to SE , the expression of IL-2R beta remained low , while that of IL2R alpha and IL2R gamma was further up-regulated , and ligand-induced tyrosine phosphorylation of Jak3 and Stat proteins was partly normalized .",
    "target_text": "After 16 hr of exposure to <protein> SE </protein> , the expression of <protein> IL-2R beta </protein> remained low , while that of <protein> IL2R alpha </protein> and <protein> IL2R gamma </protein> was further up-regulated , and ligand-induced tyrosine phosphorylation of <protein> Jak3 </protein> and <protein> Stat proteins </protein> was partly normalized ."
  },
  {
    "input_text": "Yet , IL-2 -driven proliferation remained profoundly inhibited , suggesting that signaling events other than Jak3 /Stat activation had also been changed following SE stimulation .",
    "target_text": "Yet , <protein> IL-2 </protein> -driven proliferation remained profoundly inhibited , suggesting that signaling events other than <protein> Jak3 </protein> <protein> /Stat </protein> activation had also been changed following <protein> SE </protein> stimulation ."
  },
  {
    "input_text": "In conclusion , our data suggest that SE can modulate IL-2R expression and signal transduction involving the Jak/Stat pathway in CD4+ T-cell lines .",
    "target_text": "In conclusion , our data suggest that <protein> SE </protein> can modulate <protein> IL-2R </protein> expression and signal transduction involving the <protein> Jak/Stat </protein> pathway in <cell_line> CD4+ T-cell lines </cell_line> ."
  },
  {
    "input_text": "Constitutive NF-kappa B activation , enhanced granulopoiesis , and neonatal lethality in I kappa B alpha -deficient mice .",
    "target_text": "Constitutive <protein> NF-kappa B </protein> activation , enhanced granulopoiesis , and neonatal lethality in <protein> I kappa B alpha </protein> -deficient mice ."
  },
  {
    "input_text": "Transcription factors belonging to the NF-kappa B family are controlled by inhibitory I kappa B proteins , mainly I kappa B alpha and I kappa B beta .",
    "target_text": "<protein> Transcription factors </protein> belonging to the <protein> <protein> NF-kappa B </protein> family </protein> are controlled by <protein> inhibitory I kappa B proteins </protein> , mainly <protein> I kappa B alpha </protein> and <protein> I kappa B beta </protein> ."
  },
  {
    "input_text": "Apparently normal at birth , I kappa B alpha -/- mice exhibit severe runting , skin defects , and extensive granulopoiesis postnatally , typically dying by 8 days .",
    "target_text": "Apparently normal at birth , <protein> I kappa B alpha </protein> -/- mice exhibit severe runting , skin defects , and extensive granulopoiesis postnatally , typically dying by 8 days ."
  },
  {
    "input_text": "Hematopoietic tissues from these mice display elevated levels of both nuclear NF-kappa B and mRNAs of some , but not all , genes thought to be regulated by NF-kappa B .",
    "target_text": "Hematopoietic tissues from these mice display elevated levels of both <protein> nuclear <protein> NF-kappa B </protein> </protein> and <RNA> mRNAs </RNA> of some , but not all , genes thought to be regulated by <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "NF-kappa B elevation results in these phenotypic abnormalities because mice lacking both I kappa B alpha and the p50 subunit of NF-kappa B show a dramatically delayed onset of abnormalities .",
    "target_text": "<protein> NF-kappa B </protein> elevation results in these phenotypic abnormalities because mice lacking both <protein> I kappa B alpha </protein> and the <protein> p50 subunit </protein> of <protein> NF-kappa B </protein> show a dramatically delayed onset of abnormalities ."
  },
  {
    "input_text": "In contrast to hematopoietic cells , I kappa B alpha -/- embryonic fibroblasts show minimal constitutive NF-kappa B , as well as normal signal-dependent NF-kappa B activation that is concomitant with I kappa B beta degradation .",
    "target_text": "In contrast to <cell_type> hematopoietic cells </cell_type> , <cell_line> <protein> I kappa B alpha </protein> -/- embryonic fibroblasts </cell_line> show minimal <protein> constitutive <protein> NF-kappa B </protein> </protein> , as well as normal signal-dependent <protein> NF-kappa B </protein> activation that is concomitant with <protein> I kappa B beta </protein> degradation ."
  },
  {
    "input_text": "Our results indicate that I kappa b beta , but not I kappa B alpha , is required for the signal-dependent activation of NF-kappa B in fibroblasts .",
    "target_text": "Our results indicate that I kappa b beta , but not <protein> I kappa B alpha </protein> , is required for the signal-dependent activation of <protein> NF-kappa B </protein> in <cell_type> fibroblasts </cell_type> ."
  },
  {
    "input_text": "However , I kappa B alpha is required for the postinduction repression of NF-kappa B in fibroblasts .",
    "target_text": "However , <protein> I kappa B alpha </protein> is required for the postinduction repression of <protein> NF-kappa B </protein> in <cell_type> fibroblasts </cell_type> ."
  },
  {
    "input_text": "These results define distinct roles for the two forms of I kappa B and demonstrate the necessity for stringent control of NF-kappa B .",
    "target_text": "These results define distinct roles for the two forms of <protein> I kappa B </protein> and demonstrate the necessity for stringent control of <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "Interleukin-7 can induce the activation of Jak 1 , Jak 3 and STAT 5 proteins in murine T cells .",
    "target_text": "<protein> Interleukin-7 </protein> can induce the activation of <protein> Jak 1 </protein> , <protein> Jak 3 </protein> and <protein> STAT 5 proteins </protein> in murine <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "The activation of Janus protein tyrosine kinases ( Jak ) and STAT ( signal transducer and activator of transcription ) proteins has recently been linked to the signal transduction mechanism of several cytokines .",
    "target_text": "The activation of <protein> Janus protein tyrosine kinases </protein> ( <protein> Jak </protein> ) and <protein> <protein> STAT </protein> ( <protein> signal transducer and activator of transcription </protein> ) proteins </protein> has recently been linked to the signal transduction mechanism of several <protein> cytokines </protein> ."
  },
  {
    "input_text": "IL-7 was observed to induce a rapid and dose-dependent tyrosine phosphorylation of Jak 1 and Jak 3 and concomitantly , the tyrosine phosphorylation and DNA binding activity of multiple STAT proteins .",
    "target_text": "<protein> IL-7 </protein> was observed to induce a rapid and dose-dependent tyrosine phosphorylation of <protein> Jak 1 </protein> and <protein> Jak 3 </protein> and concomitantly , the tyrosine phosphorylation and DNA binding activity of multiple <protein> STAT proteins </protein> ."
  },
  {
    "input_text": "The STAT proteins utilized by IL-7 were identical to those induced by IL-2 and could be identified as various STAT 5 isoforms .",
    "target_text": "The <protein> STAT proteins </protein> utilized by <protein> IL-7 </protein> were identical to those induced by <protein> IL-2 </protein> and could be identified as various <protein> STAT 5 isoforms </protein> ."
  },
  {
    "input_text": "Moreover , the induction of both Jak 1 and 3 , and STAT 5 activity strongly correlated with the growth-promoting effects of IL-7 , suggesting that this signal transduction mechanism may play a key role in IL-7 -induced proliferation .",
    "target_text": "Moreover , the induction of both Jak 1 and 3 , and <protein> STAT 5 </protein> activity strongly correlated with the growth-promoting effects of <protein> IL-7 </protein> , suggesting that this signal transduction mechanism may play a key role in <protein> IL-7 </protein> -induced proliferation ."
  },
  {
    "input_text": "Cytokine -modulating activity of tepoxalin , a new potential antirheumatic .",
    "target_text": "<protein> Cytokine </protein> -modulating activity of tepoxalin , a new potential antirheumatic ."
  },
  {
    "input_text": "Tepoxalin is a new dual cyclooxygenase/5-lipoxygenase anti-inflammatory compound currently under clinical investigation .",
    "target_text": "Tepoxalin is a new dual cyclooxygenase/5-lipoxygenase anti-inflammatory compound currently under clinical investigation ."
  },
  {
    "input_text": "It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit IL-2 induced signal transduction .",
    "target_text": "It has been shown to possess anti-inflammatory activity in a variety of animal models and more recently to inhibit <protein> IL-2 </protein> induced signal transduction ."
  },
  {
    "input_text": "The current study was conducted to evaluate the cytokine modulating activity of tepoxalin and the role of iron in these effects .",
    "target_text": "The current study was conducted to evaluate the <protein> cytokine </protein> modulating activity of tepoxalin and the role of iron in these effects ."
  },
  {
    "input_text": "In human peripheral blood mononuclear cells ( PBMC ) stimulated with OKT3/PMA , tepoxalin inhibited lymphocyte proliferation with an IC50 of 6 microM .",
    "target_text": "In <cell_type> human peripheral blood mononuclear cells </cell_type> ( <cell_type> PBMC </cell_type> ) stimulated with OKT3/PMA , tepoxalin inhibited <cell_type> lymphocyte </cell_type> proliferation with an IC50 of 6 microM ."
  },
  {
    "input_text": "Additionally , it inhibited the production of LTB4 ( IC50 = 0.5 microM ) and the cytokines IL-2 , IL-6 and TNF alpha ( IC50 = 10-12 microM ) .",
    "target_text": "Additionally , it inhibited the production of <protein> LTB4 </protein> ( IC50 = 0.5 microM ) and the <protein> cytokines </protein> <protein> IL-2 </protein> , <protein> IL-6 </protein> and <protein> TNF alpha </protein> ( IC50 = 10-12 microM ) ."
  },
  {
    "input_text": "Cytotoxicity was not demonstrated at these concentrations .",
    "target_text": "Cytotoxicity was not demonstrated at these concentrations ."
  },
  {
    "input_text": "Add-back experiments with either cytokines ( IL-2 or IL-6 ) , LTB4 or conditioned media failed to restore the proliferative response in the presence of tepoxalin .",
    "target_text": "Add-back experiments with either <protein> cytokines </protein> ( <protein> IL-2 </protein> or <protein> IL-6 </protein> ) , <protein> LTB4 </protein> or conditioned media failed to restore the proliferative response in the presence of tepoxalin ."
  },
  {
    "input_text": "However , the concurrent addition of iron ( in the form of ferrous or ferric chloride and other iron salts ) reversed the inhibition of proliferation caused by tepoxalin .",
    "target_text": "However , the concurrent addition of iron ( in the form of ferrous or ferric chloride and other iron salts ) reversed the inhibition of proliferation caused by tepoxalin ."
  },
  {
    "input_text": "Tepoxalin also inhibits the activation of NF kappa B , a transcription factor which acts on several cytokine genes .",
    "target_text": "Tepoxalin also inhibits the activation of <protein> NF kappa B </protein> , a <protein> transcription factor </protein> which acts on several <DNA> cytokine genes </DNA> ."
  },
  {
    "input_text": "Tepoxalin 's effect on NF kappa B is also reversed by the addition of iron salts .",
    "target_text": "Tepoxalin 's effect on <protein> NF kappa B </protein> is also reversed by the addition of iron salts ."
  },
  {
    "input_text": "These data suggest that the action of tepoxalin to inhibit proliferation in PBMC may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of NF kappa B and subsequent inhibition of cytokine production .",
    "target_text": "These data suggest that the action of tepoxalin to inhibit proliferation in <cell_type> PBMC </cell_type> may be at least in part due to its ability to reduce the amount of available iron resulting in decreased activation of <protein> NF kappa B </protein> and subsequent inhibition of <protein> cytokine </protein> production ."
  },
  {
    "input_text": "N- and C-terminal sequences control degradation of MAD3/ I kappa B alpha in response to inducers of NF-kappa B activity .",
    "target_text": "<protein> N- and C-terminal sequences </protein> control degradation of <protein> MAD3/ <protein> I kappa B alpha </protein> </protein> in response to inducers of <protein> NF-kappa B </protein> activity ."
  },
  {
    "input_text": "The proteolytic degradation of the inhibitory protein MAD3/ I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B .",
    "target_text": "The proteolytic degradation of the <protein> inhibitory protein </protein> <protein> MAD3/ <protein> I kappa B alpha </protein> </protein> in response to extracellular stimulation is a prerequisite step in the activation of the <protein> transcription factor </protein> <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that , as for the endogenous murine protein , exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity , such as phorbol myristate acetate or lipopolysaccharide .",
    "target_text": "Analysis of the expression of <protein> human <protein> I kappa B alpha </protein> protein </protein> in stable transfectants of <cell_line> mouse 70Z/3 cells </cell_line> shows that , as for the endogenous murine protein , exogenous <protein> I kappa B alpha </protein> is degraded in response to inducers of <protein> NF-kappa B </protein> activity , such as phorbol myristate acetate or lipopolysaccharide ."
  },
  {
    "input_text": "In addition , pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and , in agreement with previous studies , stabilizes a hyperphosphorylated form of the human I kappa B alpha protein .",
    "target_text": "In addition , pretreatment of the cells with the <protein> proteasome </protein> inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and , in agreement with previous studies , stabilizes a hyperphosphorylated form of the <protein> human <protein> I kappa B alpha </protein> protein </protein> ."
  },
  {
    "input_text": "By expressing mutant forms of the human protein in this cell line , we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha .",
    "target_text": "By expressing mutant forms of the human protein in this <cell_line> cell line </cell_line> , we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of <protein> I kappa B alpha </protein> ."
  },
  {
    "input_text": "Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation .",
    "target_text": "Our results show that deletion of the <protein> C terminus </protein> of the <protein> I kappa B alpha </protein> molecule up to <protein> amino acid 279 </protein> abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation ."
  },
  {
    "input_text": "Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein ( residues 32 and 36 ) and that the mutation of either residue is sufficient to abolish ligand-induced degradation , whereas both residues must be mutated to abolish inducible phosphorylation of the protein .",
    "target_text": "Further analysis reveals that the inducible phosphorylation of <protein> I kappa B alpha </protein> maps to two serines in the <protein> N terminus </protein> of the protein ( residues 32 and 36 ) and that the mutation of either residue is sufficient to abolish ligand-induced degradation , whereas both residues must be mutated to abolish inducible phosphorylation of the protein ."
  },
  {
    "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )",
    "target_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"
  },
  {
    "input_text": "Microtubules mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1,25-dihydroxyvitamin D3 in normal human monocytes .",
    "target_text": "<protein> Microtubules </protein> mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1,25-dihydroxyvitamin D3 in normal <cell_type> human monocytes </cell_type> ."
  },
  {
    "input_text": "The genomic actions of 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) are mediated by the intracellular vitamin D receptor ( VDR ) .",
    "target_text": "The genomic actions of 1,25-dihydroxyvitamin D3 ( 1,25(OH)2D3 ) are mediated by the intracellular <protein> vitamin D receptor </protein> ( <protein> VDR </protein> ) ."
  },
  {
    "input_text": "Although immunocytochemistry has shown that disruption of microtubular assembly prevents nuclear access of the sterol- VDR complex , the role of microtubules in the response to 1,25(OH)2D3 has not been studied in viable cells .",
    "target_text": "Although immunocytochemistry has shown that disruption of microtubular assembly prevents nuclear access of the <protein> sterol- <protein> VDR </protein> complex </protein> , the role of <protein> microtubules </protein> in the response to 1,25(OH)2D3 has not been studied in <cell_type> viable cells </cell_type> ."
  },
  {
    "input_text": "Our studies examined this interaction in normal human monocytes .",
    "target_text": "Our studies examined this interaction in normal <cell_type> human monocytes </cell_type> ."
  },
  {
    "input_text": "Monocytes convert 25(OH)D3 to 1,25(OH)2D3 and to 24-hydroxylated metabolites more polar than 1,25(OH)2D3 .",
    "target_text": "Monocytes convert 25(OH)D3 to 1,25(OH)2D3 and to 24-hydroxylated metabolites more polar than 1,25(OH)2D3 ."
  },
  {
    "input_text": "Microtubule disruption totally abolished the ability of exogenous 1,25(OH)2D3 to suppress its own synthesis and to induce 24-hydroxylase mRNA and activity , without affecting either total 1,25(OH)2D3 uptake or maximal 1,25(OH)2D3 -VDR binding .",
    "target_text": "Microtubule disruption totally abolished the ability of exogenous 1,25(OH)2D3 to suppress its own synthesis and to induce <RNA> 24-hydroxylase mRNA </RNA> and activity , without affecting either total 1,25(OH)2D3 uptake or maximal 1,25(OH)2D3 <protein> -VDR </protein> binding ."
  },
  {
    "input_text": "Thus , intact microtubules are essential for 1,25(OH)2D3 -dependent modulation of gene transcription .",
    "target_text": "Thus , intact <protein> microtubules </protein> are essential for 1,25(OH)2D3 -dependent modulation of gene transcription ."
  },
  {
    "input_text": "Interestingly , microtubule disruption also decreased monocyte 1,25(OH)2D3 synthesis , not by decreasing the Vmax of monocyte mitochondrial 1 alpha-hydroxylase but through an increase in the Km for 25(OH)2D3 .",
    "target_text": "Interestingly , <protein> microtubule </protein> disruption also decreased <cell_type> monocyte </cell_type> 1,25(OH)2D3 synthesis , not by decreasing the Vmax of <protein> <cell_type> monocyte </cell_type> mitochondrial 1 alpha-hydroxylase </protein> but through an increase in the Km for 25(OH)2D3 ."
  },
  {
    "input_text": "We examined 25(OH)D3 transport .",
    "target_text": "We examined 25(OH)D3 transport ."
  },
  {
    "input_text": "Microtubule disruption did not affect total cellular 25(OH)D3 uptake but reduced its intracellular trafficking to the mitochondria .",
    "target_text": "Microtubule disruption did not affect total cellular 25(OH)D3 uptake but reduced its intracellular trafficking to the mitochondria ."
  },
  {
    "input_text": "Thus , microtubules participate in intracellular 25(OH)D3 transport , and their integrity determines normal 1,25(OH)2D3 synthesis .",
    "target_text": "Thus , <protein> microtubules </protein> participate in intracellular 25(OH)D3 transport , and their integrity determines normal 1,25(OH)2D3 synthesis ."
  },
  {
    "input_text": "Relationship between Rap1 protein phosphorylation and regulation of Ca2+ transport in platelets : a new approach .",
    "target_text": "Relationship between <protein> Rap1 protein </protein> phosphorylation and regulation of Ca2+ transport in <cell_type> platelets </cell_type> : a new approach ."
  },
  {
    "input_text": "Although the interrelationship between the two messengers Ca2+ and cyclic AMP in platelet function is well documented , its mechanism of action still remains to be established .",
    "target_text": "Although the interrelationship between the two messengers Ca2+ and cyclic AMP in platelet function is well documented , its mechanism of action still remains to be established ."
  },
  {
    "input_text": "We investigated here the question of the regulation of platelet Ca(2+)-ATPases by cyclic AMP through the phosphorylation of the Rap1 protein using a pathological model .",
    "target_text": "We investigated here the question of the regulation of <protein> platelet Ca(2+)-ATPases </protein> by cyclic AMP through the phosphorylation of the <protein> Rap1 protein </protein> using a pathological model ."
  },
  {
    "input_text": "We first found experimental conditions where Ca(2+)-transport by platelet membrane vesicles appeared to be dependent on the phosphorylation of the Rap1 protein .",
    "target_text": "We first found experimental conditions where Ca(2+)-transport by platelet membrane vesicles appeared to be dependent on the phosphorylation of the <protein> Rap1 protein </protein> ."
  },
  {
    "input_text": "Then , we studied platelets of patients with congestive heart failure for their expression of the potential 97 kDa Ca(2+)-ATPase target of regulation through the Rap1 protein as well as the phosphorylation of the Rap1 protein using the catalytic subunit of the cyclic AMP -dependent protein kinase ( C. Sub. ) .",
    "target_text": "Then , we studied <cell_type> platelets </cell_type> of patients with congestive heart failure for their expression of the potential <protein> 97 kDa <protein> Ca(2+)-ATPase </protein> target </protein> of regulation through the <protein> Rap1 protein </protein> as well as the phosphorylation of the <protein> Rap1 protein </protein> using the <protein> catalytic subunit </protein> of the <protein> cyclic AMP -dependent protein kinase </protein> ( <protein> C. Sub. </protein> ) ."
  },
  {
    "input_text": "In the first patients studied , we found no significant modification in the expression of the 97 kDa Ca(2+)-ATPase by Western blotting using the PL/IM 430 monoclonal antibody which specifically recognized this isoform .",
    "target_text": "In the first patients studied , we found no significant modification in the expression of the <protein> 97 kDa Ca(2+)-ATPase </protein> by Western blotting using the <protein> PL/IM 430 monoclonal antibody </protein> which specifically recognized this isoform ."
  },
  {
    "input_text": "In contrast , the Rap1 protein was differentially phosphorylated when using 15 micrograms/ml of the C. Sub .",
    "target_text": "In contrast , the <protein> Rap1 protein </protein> was differentially phosphorylated when using 15 micrograms/ml of the <protein> C. Sub . </protein>"
  },
  {
    "input_text": "These results allowed us to use these pathological platelets to study the relationship between the expression of Rap1 protein and the regulation of Ca2+ transport by selecting a patient with severe heart failure .",
    "target_text": "These results allowed us to use these pathological <cell_type> platelets </cell_type> to study the relationship between the expression of <protein> Rap1 protein </protein> and the regulation of Ca2+ transport by selecting a patient with severe heart failure ."
  },
  {
    "input_text": "We could show a decrease in the expression as well as in the phosphorylation of Rap1 protein and demonstrate a lower effect of C. Sub. on Ca2+ transport .",
    "target_text": "We could show a decrease in the expression as well as in the phosphorylation of <protein> Rap1 protein </protein> and demonstrate a lower effect of <protein> C. Sub. </protein> on Ca2+ transport ."
  },
  {
    "input_text": "Finally , by studying a further series of patients , we could confirm that the decrease in Rap1 protein expression in heart failure , whatever its extent , was variable , and could strictly correlate the expression of Rap1 protein with the stimulatory effect of C. Sub. on Ca2+ transport .",
    "target_text": "Finally , by studying a further series of patients , we could confirm that the decrease in <protein> Rap1 protein </protein> expression in heart failure , whatever its extent , was variable , and could strictly correlate the expression of <protein> Rap1 protein </protein> with the stimulatory effect of <protein> C. Sub. </protein> on Ca2+ transport ."
  },
  {
    "input_text": "Besides the evidence for regulation of the expression of the Rap1 protein in platelets from patients with heart failure , these findings constitute a new approach in favour of the regulation of platelet Ca2+ transport through the phosphorylation of the Rap1 protein .",
    "target_text": "Besides the evidence for regulation of the expression of the <protein> Rap1 protein </protein> in <cell_type> platelets </cell_type> from patients with heart failure , these findings constitute a new approach in favour of the regulation of platelet Ca2+ transport through the phosphorylation of the <protein> Rap1 protein </protein> ."
  },
  {
    "input_text": "An IRF-1 -dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes .",
    "target_text": "An <protein> IRF-1 </protein> -dependent pathway of DNA damage-induced apoptosis in <cell_line> mitogen-activated T lymphocytes </cell_line> ."
  },
  {
    "input_text": "Lymphocytes are particularly susceptible to DNA damage-induced apoptosis , a response which may serve as a form of ' altruistic suicide ' to counter their intrinsic high potential for mutation and clonal expansion .",
    "target_text": "<cell_line> Lymphocytes </cell_line> are particularly susceptible to DNA damage-induced apoptosis , a response which may serve as a form of ' altruistic suicide ' to counter their intrinsic high potential for mutation and clonal expansion ."
  },
  {
    "input_text": "The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes , but an as yet unknown , p53 -independent pathway ( s ) appears to mediate the same event in mitogen-activated mature T lymphocytes .",
    "target_text": "The <protein> tumour suppressor p53 </protein> has been shown to regulate this type of apoptosis in <cell_type> thymocytes </cell_type> , but an as yet unknown , <protein> p53 </protein> -independent pathway ( s ) appears to mediate the same event in <cell_line> mitogen-activated mature T lymphocytes </cell_line> ."
  },
  {
    "input_text": "Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor ( IRF ) -1 .",
    "target_text": "Here we show DNA damage-induced apoptosis in these <cell_type> T lymphocytes </cell_type> is dependent on the <protein> antioncogenic <protein> transcription factor </protein> interferon regulatory factor </protein> <protein> ( IRF ) -1 </protein> ."
  },
  {
    "input_text": "Thus two different anti-onco-genic transcription factors , p53 and IRF-1 , are required for distinct apoptotic pathways in T lymphocytes .",
    "target_text": "Thus two different <protein> anti-onco-genic transcription factors </protein> , <protein> p53 </protein> and <protein> IRF-1 </protein> , are required for distinct apoptotic pathways in <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "We also show that mitogen induction of the interleukin-1 beta converting enzyme ( ICE ) gene , a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3 , is IRF-1 -dependent .",
    "target_text": "We also show that mitogen induction of the <DNA> <protein> interleukin-1 beta converting enzyme </protein> ( <protein> ICE </protein> ) gene </DNA> , a <protein> mammalian homologue </protein> of the <DNA> Caenorhabditis elegans cell death gene </DNA> <DNA> ced-3 </DNA> , is <protein> IRF-1 </protein> -dependent ."
  },
  {
    "input_text": "Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis .",
    "target_text": "Ectopic overexpression of <protein> IRF-1 </protein> results in the activation of the <DNA> endogenous gene </DNA> for <protein> ICE </protein> and enhances the sensitivity of cells to radiation-induced apoptosis ."
  },
  {
    "input_text": "Circadian rhythm of glucocorticoid receptors in human peripheral leukocytes and their reactivity to glucocorticoids .",
    "target_text": "Circadian rhythm of <protein> glucocorticoid receptors </protein> in <cell_type> human peripheral leukocytes </cell_type> and their reactivity to glucocorticoids ."
  },
  {
    "input_text": "1 ) There exists a CR of GR in human leukocytes , PMN , and monocytes with the peak values from 0400 to 0800 hr and the trough values between 2300 and 0000 hr .",
    "target_text": "1 ) There exists a CR of <protein> GR </protein> in <cell_type> human leukocytes </cell_type> , <cell_type> PMN </cell_type> , and <cell_type> monocytes </cell_type> with the peak values from 0400 to 0800 hr and the trough values between 2300 and 0000 hr ."
  },
  {
    "input_text": "The difference between them was significant statistically .",
    "target_text": "The difference between them was significant statistically ."
  },
  {
    "input_text": "2 ) The FI of the chemotactic migration rate of PMN by cortisol also showed diurnal changes which were synchronous with that of GR .",
    "target_text": "2 ) The FI of the chemotactic migration rate of <cell_type> PMN </cell_type> by cortisol also showed diurnal changes which were synchronous with that of <protein> GR </protein> ."
  },
  {
    "input_text": "This indicates that the CR of GR may be of functional significance .",
    "target_text": "This indicates that the CR of <protein> GR </protein> may be of functional significance ."
  },
  {
    "input_text": "3 ) In Cushing 's syndrome , the CR of GR was normal in spite of the fact that the CR of plasma cortisol was disturbed .",
    "target_text": "3 ) In Cushing 's syndrome , the CR of <protein> GR </protein> was normal in spite of the fact that the CR of plasma cortisol was disturbed ."
  },
  {
    "input_text": "This indicates the independency of the CR of GR from that of cortisol .",
    "target_text": "This indicates the independency of the CR of <protein> GR </protein> from that of cortisol ."
  },
  {
    "input_text": "4 ) In apoplexy caused by brain ischemia , the CR of GR was abolished in patients with basal lesions but preserved when the lesions were located in the cerebral cortex .",
    "target_text": "4 ) In apoplexy caused by brain ischemia , the CR of <protein> GR </protein> was abolished in patients with basal lesions but preserved when the lesions were located in the cerebral cortex ."
  },
  {
    "input_text": "These results strongly suggest that the main \" circadian pacemaker \" of GR is located in the basal brain , most probably in the suprachiasmatic nuclei as has been suggested for rodents .",
    "target_text": "These results strongly suggest that the main \" circadian pacemaker \" of <protein> GR </protein> is located in the basal brain , most probably in the suprachiasmatic nuclei as has been suggested for rodents ."
  },
  {
    "input_text": "B-lymphoblastoid cell lines from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus .",
    "target_text": "<cell_line> B-lymphoblastoid cell lines </cell_line> from multiple sclerosis patients and a healthy control producing a putative new human retrovirus and Epstein-Barr virus ."
  },
  {
    "input_text": "On several occasions we have observed retrovirus-like particles ( RVLPs ) by transmission electron microscopy ( EM ) of cultured T cells from a patient with MS .",
    "target_text": "On several occasions we have observed retrovirus-like particles ( RVLPs ) by transmission electron microscopy ( EM ) of <cell_line> cultured T cells </cell_line> from a patient with MS ."
  },
  {
    "input_text": "Later we established spontaneously formed B-lymphoblastoid cell lines ( LCLs ) from a patient with an MS -like disease and from another patient with MS who had a reactivated Epstein-Barr virus ( EBV ) infection .",
    "target_text": "Later we established spontaneously formed <cell_line> B-lymphoblastoid cell lines </cell_line> ( <cell_line> LCLs </cell_line> ) from a patient with an MS -like disease and from another patient with MS who had a reactivated Epstein-Barr virus ( EBV ) infection ."
  },
  {
    "input_text": "Both LCLs were found by EM to produce RVLP and EBV particles .",
    "target_text": "Both <cell_line> LCLs </cell_line> were found by EM to produce RVLP and EBV particles ."
  },
  {
    "input_text": "Reverse transcriptase ( RT ) assays were positive in purified viral material from both LCLs .",
    "target_text": "Reverse transcriptase ( RT ) assays were positive in purified viral material from both <cell_line> LCLs </cell_line> ."
  },
  {
    "input_text": "To substantiate these findings we initiated an intensified culturing procedure and were able to establish LCLs from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls .",
    "target_text": "To substantiate these findings we initiated an intensified culturing procedure and were able to establish <cell_line> LCLs </cell_line> from 5 out of 21 consecutive MS patients and 1 out of 13 consecutive healthy controls ."
  },
  {
    "input_text": "All LCLs were found to produce both RVLP and EBV particles by EM .",
    "target_text": "All <cell_line> LCLs </cell_line> were found to produce both RVLP and EBV particles by EM ."
  },
  {
    "input_text": "Whether the putative new retrovirus ( es ) and EBV have any causal relationship to MS is still not known , but the findings support this possibility .",
    "target_text": "Whether the putative new retrovirus ( es ) and EBV have any causal relationship to MS is still not known , but the findings support this possibility ."
  },
  {
    "input_text": "Identification of an ionomycin /cyclosporin A -responsive element within the human T cell receptor gamma enhancer .",
    "target_text": "Identification of an <DNA> ionomycin /cyclosporin A -responsive element </DNA> within the <DNA> human T cell receptor gamma enhancer </DNA> ."
  },
  {
    "input_text": "Activation through the Ca2+ / calcineurin pathway is essential to the transcription of many cytokine genes .",
    "target_text": "Activation through the Ca2+ / <protein> calcineurin </protein> pathway is essential to the transcription of many <DNA> cytokine genes </DNA> ."
  },
  {
    "input_text": "The conserved cis-acting sequence , GGAAAA , and transcription factors binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations .",
    "target_text": "The <DNA> conserved cis-acting sequence </DNA> , GGAAAA , and <protein> transcription factors </protein> binding to this sequence are involved in the response to increased intracellular Ca2+ concentrations ."
  },
  {
    "input_text": "Here we report the identification and importance of the same sequence in a non-cytokine gene , the human T cell receptor gamma ( TCRG ) enhancer .",
    "target_text": "Here we report the identification and importance of the same sequence in a <DNA> non-cytokine gene </DNA> , the <DNA> <protein> <cell_type> human T cell </cell_type> receptor gamma </protein> ( <protein> TCRG </protein> ) enhancer </DNA> ."
  },
  {
    "input_text": "Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin -induced activation of the TCRG enhancer .",
    "target_text": "Results from site-directed mutations and electrophoretic mobility shift assays strongly suggest that this sequence mediates the ionomycin -induced activation of the <DNA> TCRG enhancer </DNA> ."
  },
  {
    "input_text": "Our studies provide an explanation for a previous observation that TCRG mRNA levels , but not mRNA levels for T cell receptor alpha and -beta , are increased by ionomycin treatment .",
    "target_text": "Our studies provide an explanation for a previous observation that <RNA> TCRG mRNA </RNA> levels , but not mRNA levels for T cell receptor alpha and -beta , are increased by ionomycin treatment ."
  },
  {
    "input_text": "Coexpression of NF-kappa B /Rel and Sp1 transcription factors in human immunodeficiency virus 1 -induced , dendritic cell-T-cell syncytia .",
    "target_text": "Coexpression of <protein> <protein> NF-kappa B </protein> /Rel </protein> and <protein> Sp1 </protein> <protein> transcription factors </protein> in human immunodeficiency virus 1 -induced , dendritic cell-T-cell syncytia ."
  },
  {
    "input_text": "Productive infection of T cells with human immunodeficiency virus 1 ( HIV-1 ) typically requires that the T cells be stimulated with antigens or mitogens .",
    "target_text": "Productive infection of <cell_type> T cells </cell_type> with human immunodeficiency virus 1 ( HIV-1 ) typically requires that the <cell_type> T cells </cell_type> be stimulated with antigens or mitogens ."
  },
  {
    "input_text": "This requirement has been attributed to the activation of the transcription factor NF-kappa B , which synergizes with the constitutive transcription factor Sp1 to drive the HIV-1 promoter .",
    "target_text": "This requirement has been attributed to the activation of the <protein> transcription factor </protein> <protein> NF-kappa B </protein> , which synergizes with the <protein> constitutive transcription factor </protein> <protein> Sp1 </protein> to drive the <DNA> HIV-1 promoter </DNA> ."
  },
  {
    "input_text": "Recently , we have found that vigorous replication of HIV-1 takes place in nonactivated memory T cells after syncytium formation with dendritic cells ( DCs ) .",
    "target_text": "Recently , we have found that vigorous replication of HIV-1 takes place in nonactivated <cell_type> memory <cell_type> T cells </cell_type> </cell_type> after syncytium formation with <cell_type> dendritic cells </cell_type> ( <cell_type> DCs </cell_type> ) ."
  },
  {
    "input_text": "These syncytia lack activated cells as determined by an absence of staining for Ki-67 cell cycle antigen .",
    "target_text": "These syncytia lack <cell_type> activated cells </cell_type> as determined by an absence of staining for Ki-67 cell cycle antigen ."
  },
  {
    "input_text": "The expression and activity of NF-kappa B and Sp1 were , therefore , analyzed in isolated T cells and DCs from humans and mice .",
    "target_text": "The expression and activity of <protein> NF-kappa B </protein> and <protein> Sp1 </protein> were , therefore , analyzed in isolated <cell_type> T cells </cell_type> and <cell_type> DCs </cell_type> from humans and mice ."
  },
  {
    "input_text": "We have used immunolabeling , Western blot analysis , and electrophoretic mobility shift and supershift assays .",
    "target_text": "We have used immunolabeling , Western blot analysis , and electrophoretic mobility shift and supershift assays ."
  },
  {
    "input_text": "T cells lack active NF-kappa B but express Sp1 as expected .",
    "target_text": "<cell_type> T cells </cell_type> lack active <protein> NF-kappa B </protein> but express <protein> Sp1 </protein> as expected ."
  },
  {
    "input_text": "DCs express high levels of all known NF-kappa B and Rel proteins , with activity residing primarily within RelB , p50 , and p65 .",
    "target_text": "<cell_type> DCs </cell_type> express high levels of all known <protein> NF-kappa B </protein> and <protein> Rel proteins </protein> , with activity residing primarily within <protein> RelB </protein> , <protein> p50 </protein> , and <protein> p65 </protein> ."
  },
  {
    "input_text": "However , DCs lack Sp1 , which may explain the failure of HIV-1 to replicate in purified DCs .",
    "target_text": "However , <cell_type> DCs </cell_type> lack <protein> Sp1 </protein> , which may explain the failure of HIV-1 to replicate in purified <cell_type> DCs </cell_type> ."
  },
  {
    "input_text": "Coexpression of NF-kappa B and Sp1 occurs in the heterologous DC-T-cell syncytia that are induced by HIV-1 .",
    "target_text": "Coexpression of <protein> NF-kappa B </protein> and <protein> Sp1 </protein> occurs in the <cell_type> heterologous DC-T-cell syncytia </cell_type> that are induced by HIV-1 ."
  },
  {
    "input_text": "Therefore , HIV-1 -induced cell fusion brings together factors that upregulate virus transcription .",
    "target_text": "Therefore , HIV-1 -induced cell fusion brings together factors that upregulate virus transcription ."
  },
  {
    "input_text": "Since DCs and memory T cells frequently traffic together in situ , these unusual heterologous syncytia could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation .",
    "target_text": "Since <cell_type> DCs </cell_type> and memory <cell_type> T cells </cell_type> frequently traffic together in situ , these unusual <cell_type> heterologous syncytia </cell_type> could develop in infected individuals and lead to chronic HIV-1 replication without ostensible immune stimulation ."
  },
  {
    "input_text": "Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha .",
    "target_text": "Cupric ion blocks <protein> NF kappa B </protein> activation through inhibiting the signal-induced phosphorylation of <protein> I kappa B alpha </protein> ."
  },
  {
    "input_text": "A transcription factor NF kappa B , which regulates expression of various cellular genes involved in immune responses and viral genes including HIV , is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B .",
    "target_text": "A <protein> transcription factor </protein> <protein> NF kappa B </protein> , which regulates expression of various cellular genes involved in immune responses and <DNA> viral genes </DNA> including HIV , is sequestered in the cytoplasm as a complex with an <protein> inhibitory protein I kappa B </protein> ."
  },
  {
    "input_text": "Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B .",
    "target_text": "Various extracellular signals induce phosphorylation and rapid degradation of <protein> I kappa B alpha </protein> to release <protein> NF kappa B </protein> ."
  },
  {
    "input_text": "Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha , TPA , or H2O2 .",
    "target_text": "Cu2+ was found to inhibit the activation of <protein> NF kappa B </protein> induced by <protein> TNF-alpha </protein> , TPA , or H2O2 ."
  },
  {
    "input_text": "Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha , indicating that Cu2+ interferes with the dissociation of the NF kappa B -I kappa B complex .",
    "target_text": "Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by <protein> TNF-alpha </protein> in the presence of Cu2+ resulted in the release of <protein> NF kappa B </protein> from <protein> I kappa B alpha </protein> , indicating that Cu2+ interferes with the dissociation of the <protein> <protein> NF kappa B </protein> -I kappa B complex </protein> ."
  },
  {
    "input_text": "Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+ .",
    "target_text": "Neither phosphorylation nor degradation of <protein> I kappa B alpha </protein> was observed upon <protein> TNF-alpha </protein> stimulation in the presence of Cu2+ ."
  },
  {
    "input_text": "These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha .",
    "target_text": "These results indicate that Cu2+ inhibits the release of <protein> NF kappa B </protein> by blockade of a signal leading to the phosphorylation of <protein> I kappa B alpha </protein> ."
  },
  {
    "input_text": "Cloning a cDNA from human NK/ T cells which codes for a protein with high proline content .",
    "target_text": "Cloning a <DNA> cDNA </DNA> from human <cell_type> NK/ <cell_type> T cells </cell_type> </cell_type> which codes for a protein with high proline content ."
  },
  {
    "input_text": "A cDNA clone , B4-2 , was isolated from a natural killer ( NK ) minus T cell subtractive library .",
    "target_text": "A <DNA> cDNA clone </DNA> , <DNA> B4-2 </DNA> , was isolated from a <DNA> natural killer ( NK ) minus T cell subtractive library </DNA> ."
  },
  {
    "input_text": "The B4-2 clone coded for an mRNA of 2061 bp in length .",
    "target_text": "The <DNA> B4-2 </DNA> clone coded for an <RNA> mRNA </RNA> of 2061 bp in length ."
  },
  {
    "input_text": "It encodes a deduced 327 aa protein with a calculated molecular mass of 35.2 kDa .",
    "target_text": "It encodes a deduced <protein> 327 aa protein </protein> with a calculated molecular mass of 35.2 kDa ."
  },
  {
    "input_text": "Searching of B4-2 DNA and protein sequences against various databases revealed no high homology to other sequences .",
    "target_text": "Searching of <DNA> <DNA> B4-2 </DNA> DNA </DNA> and protein sequences against various databases revealed no high homology to other sequences ."
  },
  {
    "input_text": "However , B4-2 has an unusually high proline content ( 13 % ) , contains a putative nuclear targeting sequence , and has several SPXX motifs which are frequently found in gene regulatory proteins .",
    "target_text": "However , <DNA> B4-2 </DNA> has an unusually high proline content ( 13 % ) , contains a putative <protein> nuclear targeting sequence </protein> , and has several <protein> SPXX motifs </protein> which are frequently found in <protein> gene regulatory proteins </protein> ."
  },
  {
    "input_text": "One of the stretches of prolines in B4-2 closely resembles the ligand for proteins with SH3 domains .",
    "target_text": "One of the stretches of prolines in <DNA> B4-2 </DNA> closely resembles the ligand for proteins with <protein> SH3 domains </protein> ."
  },
  {
    "input_text": "Northern hybridization data showed that B4-2 is not a lymphoid specific gene and is expressed in a hepatoma cell line and also weakly transcribed or absent in a variety of other cells .",
    "target_text": "Northern hybridization data showed that <DNA> B4-2 </DNA> is not a <DNA> lymphoid specific gene </DNA> and is expressed in a <cell_line> hepatoma cell line </cell_line> and also weakly transcribed or absent in a variety of other cells ."
  },
  {
    "input_text": "A polyclonal antiserum raised against recombinant B4-2 recognizes a 32-34 kDa protein in lymphocytes .",
    "target_text": "A polyclonal antiserum raised against <protein> recombinant <DNA> B4-2 </DNA> </protein> recognizes a <protein> 32-34 kDa protein </protein> in <cell_type> lymphocytes </cell_type> ."
  },
  {
    "input_text": "Activation of JAK3 , but not JAK1 , is critical for IL-2 -induced proliferation and STAT5 recruitment by a COOH-terminal region of the IL-2 receptor beta-chain .",
    "target_text": "Activation of <protein> JAK3 </protein> , but not <protein> JAK1 </protein> , is critical for <protein> IL-2 </protein> -induced proliferation and <protein> STAT5 </protein> recruitment by a <protein> COOH-terminal region </protein> of the <protein> IL-2 receptor beta-chain </protein> ."
  },
  {
    "input_text": "A number of cytokines and growth factors use the JAK -STAT pathway to signal from the cell membrane to the nucleus .",
    "target_text": "A number of <protein> cytokines </protein> and <protein> growth factors </protein> use the <protein> JAK </protein> <protein> -STAT </protein> pathway to signal from the cell membrane to the nucleus ."
  },
  {
    "input_text": "While homodimerizing cytokine receptors may transmit signal via a single form of JAK ( i.e. growth hormone receptors ) , several multicomponent cytokine receptors have been shown to require simultaneous activation of pairs of different JAK kinases ( i.e. interferon receptors ) .",
    "target_text": "While <protein> homodimerizing cytokine receptors </protein> may transmit signal via a single form of <protein> JAK </protein> ( i.e. <protein> growth hormone receptors </protein> ) , several <protein> multicomponent cytokine receptors </protein> have been shown to require simultaneous activation of pairs of different <protein> JAK kinases </protein> ( i.e. <protein> interferon receptors </protein> ) ."
  },
  {
    "input_text": "Recent evidence for a preferential coupling of JAK3 to interleukin-2 receptor-gamma ( IL-2R gamma ) and JAK1 to IL-2R beta supports the concept of heterotrans-activation of JAK1 and JAK3 caused by IL-2 -induced heterodimerization of their receptor partners .",
    "target_text": "Recent evidence for a preferential coupling of <protein> JAK3 </protein> to <protein> interleukin-2 receptor-gamma </protein> ( <protein> IL-2R gamma </protein> ) and <protein> JAK1 </protein> to <protein> IL-2R beta </protein> supports the concept of heterotrans-activation of <protein> JAK1 </protein> and <protein> JAK3 </protein> caused by <protein> IL-2 </protein> -induced heterodimerization of their receptor partners ."
  },
  {
    "input_text": "The present study verified the ability of IL-2 to cause tyrosine phosphorylation and activation of JAK1 and JAK3 , but demonstrated that IL-2 stimulated JAK3 to a significantly larger extent than JAK1 in human T lymphocytes and the YT cell line .",
    "target_text": "The present study verified the ability of <protein> IL-2 </protein> to cause tyrosine phosphorylation and activation of <protein> JAK1 </protein> and <protein> JAK3 </protein> , but demonstrated that <protein> IL-2 </protein> stimulated <protein> JAK3 </protein> to a significantly larger extent than <protein> JAK1 </protein> in <cell_type> human T lymphocytes </cell_type> and the <cell_line> YT cell line </cell_line> ."
  },
  {
    "input_text": "This conclusion was based upon several independent criteria , including more vigorous tyrosine phosphorylation of JAK3 , more marked enzymatic activation of JAK3 as well as higher abundance of JAK3 in activated IL-2 receptor complexes .",
    "target_text": "This conclusion was based upon several independent criteria , including more vigorous tyrosine phosphorylation of <protein> JAK3 </protein> , more marked enzymatic activation of <protein> JAK3 </protein> as well as higher abundance of <protein> JAK3 </protein> in activated <protein> IL-2 receptor complexes </protein> ."
  },
  {
    "input_text": "Furthermore , when human IL-2R beta was stably expressed in murine BA/F3 cells , robust IL-2 -induced proliferation and JAK3 activation occurred without detectable involvement of either JAK1 , JAK2 or TYK2 .",
    "target_text": "Furthermore , when <protein> human <protein> IL-2R </protein> beta </protein> was stably expressed in <cell_line> murine BA/F3 cells </cell_line> , robust <protein> IL-2 </protein> -induced proliferation and <protein> JAK3 </protein> activation occurred without detectable involvement of either <protein> JAK1 </protein> , <protein> JAK2 </protein> or <protein> TYK2 </protein> ."
  },
  {
    "input_text": "We therefore propose that IL-2 receptor signal transduction does not depend on equimolar heterodimerization of JAK1 and JAK3 following IL-2 -induced heterodimerization of IL-2R beta and IL-2R gamma .",
    "target_text": "We therefore propose that <protein> <protein> IL-2 </protein> receptor </protein> signal transduction does not depend on equimolar heterodimerization of <protein> JAK1 </protein> and <protein> JAK3 </protein> following <protein> IL-2 </protein> -induced heterodimerization of <protein> <protein> IL-2R </protein> beta </protein> and <protein> IL-2R gamma </protein> ."
  },
  {
    "input_text": "Nonetheless , a membrane-proximal region of human IL-2R beta ( Asn240-Leu335 ) was critical for JAK3 activation , and the amount of JAK3 present in activated IL-2 receptor complexes increased with time , suggesting that stabilization of JAK3 binding to the receptor complex relies on both IL-2R beta and IL-2R gamma .",
    "target_text": "Nonetheless , a <protein> membrane-proximal region </protein> of human <protein> IL-2R beta </protein> ( <protein> Asn240-Leu335 </protein> ) was critical for <protein> JAK3 </protein> activation , and the amount of <protein> JAK3 </protein> present in activated <protein> <protein> IL-2 </protein> receptor complexes </protein> increased with time , suggesting that stabilization of <protein> JAK3 </protein> binding to the <protein> receptor complex </protein> relies on both <protein> IL-2R beta </protein> and <protein> IL-2R gamma </protein> ."
  },
  {
    "input_text": "Moreover , STAT5 was found to be the predominant STAT transcription factor used by IL-2 in human T cells , and specifically required a COOH-terminal region of IL-2R beta ( Ser386-Val525 ) , while STAT5 recruitment was not correlated to activation of IL-2R gamma or JAK3 .",
    "target_text": "Moreover , <protein> STAT5 </protein> was found to be the predominant <protein> STAT transcription factor </protein> used by <protein> IL-2 </protein> in <cell_type> human <cell_type> T cells </cell_type> </cell_type> , and specifically required a <protein> COOH-terminal region </protein> of <protein> IL-2R beta </protein> ( <protein> Ser386-Val525 </protein> ) , while <protein> STAT5 </protein> recruitment was not correlated to activation of <protein> IL-2R gamma </protein> or <protein> JAK3 </protein> ."
  },
  {
    "input_text": "Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated human T lymphocytes .",
    "target_text": "Up-regulation of high-affinity dehydroepiandrosterone binding activity by dehydroepiandrosterone in activated <cell_type> human T lymphocytes </cell_type> ."
  },
  {
    "input_text": "Although evidence indicates that dehydroepiandrosterone ( DHEA ) exerts direct physiological effects , its mechanism of action remains unknown .",
    "target_text": "Although evidence indicates that dehydroepiandrosterone ( DHEA ) exerts direct physiological effects , its mechanism of action remains unknown ."
  },
  {
    "input_text": "DHEA binding sites were examined using a whole-cell binding assay in a human T lymphoid cell line , PEER , revealing that a single class of high-affinity binding sites for DHEA ( dissociation constant = 7.4 +/- 0.53 nmol/L , mean +/- SE , n = 4 ) was greatly increased when treated with DHEA , phorbol-12-myristate-13-acetate , and the Ca2+ ionophore A23187 .",
    "target_text": "DHEA binding sites were examined using a whole-cell binding assay in a <cell_line> human T lymphoid cell line </cell_line> , <cell_line> PEER </cell_line> , revealing that a single class of high-affinity binding sites for DHEA ( dissociation constant = 7.4 +/- 0.53 nmol/L , mean +/- SE , n = 4 ) was greatly increased when treated with DHEA , phorbol-12-myristate-13-acetate , and the Ca2+ ionophore A23187 ."
  },
  {
    "input_text": "Bound [3H] DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone , but not effectively by other steroids , including DHEA sulfate .",
    "target_text": "Bound [3H] DHEA was displaced sensitively by DHEA and secondarily by dihydrotestosterone , but not effectively by other steroids , including DHEA sulfate ."
  },
  {
    "input_text": "These results not only indicate the existence of a DHEA receptor , but also suggest that T cells become susceptible to regulation by DHEA during the process of signal-induced activation .",
    "target_text": "These results not only indicate the existence of a <protein> DHEA receptor </protein> , but also suggest that <cell_type> T cells </cell_type> become susceptible to regulation by DHEA during the process of signal-induced activation ."
  },
  {
    "input_text": "Ubiquitin-mediated processing of NF-kappa B transcriptional activator precursor p105 .",
    "target_text": "Ubiquitin-mediated processing of <protein> NF-kappa B </protein> <protein> transcriptional activator precursor </protein> <protein> p105 </protein> ."
  },
  {
    "input_text": "Reconstitution of a cell-free system and identification of the ubiquitin-carrier protein , E2 , and a novel ubiquitin-protein ligase , E3 , involved in conjugation .",
    "target_text": "Reconstitution of a cell-free system and identification of the <protein> ubiquitin-carrier protein </protein> , <protein> E2 </protein> , and a novel <protein> ubiquitin-protein ligase </protein> , <protein> E3 </protein> , involved in conjugation ."
  },
  {
    "input_text": "In most cases , the transcriptional factor NF-kappa B is a heterodimer consisting of two subunits , p50 and p65 , which are encoded by two distinct genes of the Rel family .",
    "target_text": "In most cases , the <protein> transcriptional factor </protein> <protein> NF-kappa B </protein> is a <protein> heterodimer </protein> consisting of two subunits , <protein> p50 </protein> and <protein> p65 </protein> , which are encoded by two distinct genes of the <DNA> Rel family </DNA> ."
  },
  {
    "input_text": "p50 is translated as a precursor of 105 kDa .",
    "target_text": "<protein> p50 </protein> is translated as a precursor of <protein> 105 kDa </protein> ."
  },
  {
    "input_text": "The C-terminal domain of the precursor is rapidly degraded , forming the mature p50 subunit consisted of the N-terminal region of the molecule .",
    "target_text": "The <protein> C-terminal domain </protein> of the precursor is rapidly degraded , forming the <protein> mature p50 subunit </protein> consisted of the <protein> N-terminal region </protein> of the molecule ."
  },
  {
    "input_text": "The mechanism of generation of p50 is not known .",
    "target_text": "The mechanism of generation of <protein> p50 </protein> is not known ."
  },
  {
    "input_text": "It has been suggested that the ubiquitin -proteasome system is involved in the process ; however , the specific enzymes involved and the mechanism of limited proteolysis , in which half of the molecule is spared , have been obscure .",
    "target_text": "It has been suggested that the <protein> ubiquitin </protein> <protein> -proteasome </protein> system is involved in the process ; however , the specific <protein> enzymes </protein> involved and the mechanism of limited proteolysis , in which half of the molecule is spared , have been obscure ."
  },
  {
    "input_text": "Palombella and colleagues ( Palombella , V.J. , Rando , O.J. , Goldberg , A.L. , and Maniatis , T. ( 1994 ) Cell 78 , 773-785 ) have shown that ubiquitin is required for the processing in a cell-free system of a truncated , artificially constructed , 60-kDa precursor .",
    "target_text": "Palombella and colleagues ( Palombella , V.J. , Rando , O.J. , Goldberg , A.L. , and Maniatis , T. ( 1994 ) Cell 78 , 773-785 ) have shown that <protein> ubiquitin </protein> is required for the processing in a cell-free system of a truncated , artificially constructed , <protein> 60-kDa precursor </protein> ."
  },
  {
    "input_text": "They have also shown that proteasome inhibitors block the processing both in vitro and in vivo .",
    "target_text": "They have also shown that <protein> proteasome </protein> inhibitors block the processing both in vitro and in vivo ."
  },
  {
    "input_text": "In this study , we demonstrate reconstitution of a cell-free processing system and demonstrate directly that : ( a ) the ubiquitin -proteasome system is involved in processing of the intact p105 precursor , ( b ) conjugation of ubiquitin to the precursor is an essential intermediate step in the processing , ( c ) the recently discovered novel species of the ubiquitin -carrier protein , E2-F1 , that is involved in the conjugation and degradation of p53 , is also required for the limited processing of the p105 precursor , and ( d ) a novel , approximately 320-kDa species of ubiquitin -protein ligase , is involved in the process .",
    "target_text": "In this study , we demonstrate reconstitution of a cell-free processing system and demonstrate directly that : ( a ) the <protein> ubiquitin </protein> <protein> -proteasome </protein> system is involved in processing of the intact <protein> p105 </protein> precursor , ( b ) conjugation of <protein> ubiquitin </protein> to the precursor is an essential intermediate step in the processing , ( c ) the recently discovered novel species of the <protein> <protein> ubiquitin </protein> -carrier protein </protein> , <protein> E2-F1 </protein> , that is involved in the conjugation and degradation of <protein> p53 </protein> , is also required for the limited processing of the <protein> p105 precursor </protein> , and ( d ) a novel , approximately <protein> 320-kDa species </protein> of <protein> <protein> ubiquitin </protein> -protein ligase </protein> , is involved in the process ."
  },
  {
    "input_text": "This novel enzyme is distinct from E6-AP , the p53 -conjugating ligase , and from E3 alpha , the \" N-end rule \" ligase .",
    "target_text": "This novel enzyme is distinct from <protein> E6-AP </protein> , the <protein> <protein> p53 </protein> -conjugating ligase </protein> , and from <protein> <protein> E3 </protein> alpha </protein> , the <protein> \" N-end rule \" ligase </protein> ."
  },
  {
    "input_text": "Flutamide in the treatment of hirsutism : long-term clinical effects , endocrine changes , and androgen receptor behavior .",
    "target_text": "Flutamide in the treatment of hirsutism : long-term clinical effects , endocrine changes , and <protein> androgen receptor </protein> behavior ."
  },
  {
    "input_text": "OBJECTIVE : To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters , as well as on the androgen receptor status , in hirsute women .",
    "target_text": "OBJECTIVE : To investigate the long-term effects of treatment with low doses of flutamide on clinical and hormonal parameters , as well as on the <protein> androgen receptor </protein> status , in hirsute women ."
  },
  {
    "input_text": "DESIGN : Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide , three times per day for 12 months .",
    "target_text": "DESIGN : Eighteen hirsute patients with regular menses were studied basally and during treatment with 125 mg flutamide , three times per day for 12 months ."
  },
  {
    "input_text": "Barrier or intrauterine contraception was used during the study in sexually active women .",
    "target_text": "Barrier or intrauterine contraception was used during the study in sexually active women ."
  },
  {
    "input_text": "Safety parameters were assessed throughout the study .",
    "target_text": "Safety parameters were assessed throughout the study ."
  },
  {
    "input_text": "Hirsutism , graded by the modified Ferriman-Gallwey score , and hormonal parameters were evaluated basally and at 4-month intervals during treatment .",
    "target_text": "Hirsutism , graded by the modified Ferriman-Gallwey score , and hormonal parameters were evaluated basally and at 4-month intervals during treatment ."
  },
  {
    "input_text": "Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy .",
    "target_text": "Gonadotropin-releasing hormone and ACTH stimulation tests were performed before and after 3 to 4 months of therapy ."
  },
  {
    "input_text": "In addition , the concentration of androgen receptors in mononuclear leukocytes was measured , in both the follicular and luteal phases of the menstrual cycle , basally and after 4 months of flutamide treatment .",
    "target_text": "In addition , the concentration of <protein> androgen receptors </protein> in <cell_type> mononuclear leukocytes </cell_type> was measured , in both the follicular and luteal phases of the menstrual cycle , basally and after 4 months of flutamide treatment ."
  },
  {
    "input_text": "RESULTS : Flutamide was well tolerated in all women , with the noticeable exception of one patient who presented increased serum transaminase after 8 months of therapy .",
    "target_text": "RESULTS : Flutamide was well tolerated in all women , with the noticeable exception of one patient who presented increased <protein> serum transaminase </protein> after 8 months of <protein> therapy </protein> ."
  },
  {
    "input_text": "Hirsutism markedly improved in all women during the treatment ( Ferriman-Gallwey score after 1 year : 4.1 +/- 0.5 versus 14.1 +/- 0.9 ) .",
    "target_text": "Hirsutism markedly improved in all women during the treatment ( Ferriman-Gallwey score after 1 year : 4.1 +/- 0.5 versus 14.1 +/- 0.9 ) ."
  },
  {
    "input_text": "A reduction of serum androgens was found , whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH .",
    "target_text": "A reduction of serum androgens was found , whereas no change was observed in either basal or GnRH-stimulated gonadotropins or in the cortisol and 17 alpha-hydroxyprogesterone response to ACTH ."
  },
  {
    "input_text": "Cycles remained ovulatory .",
    "target_text": "Cycles remained ovulatory ."
  },
  {
    "input_text": "Before treatment , the number of androgen receptors was higher in the luteal than in the follicular phase .",
    "target_text": "Before treatment , the number of <protein> androgen receptors </protein> was higher in the luteal than in the follicular phase ."
  },
  {
    "input_text": "This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug .",
    "target_text": "This rhythmic differentiation disappeared after the patients had been given the antiandrogen drug ."
  },
  {
    "input_text": "CONCLUSIONS : Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function .",
    "target_text": "CONCLUSIONS : Flutamide is effective in the treatment of hirsutism but requires constant surveillance of liver function ."
  },
  {
    "input_text": "Androgen receptor blockade might be potentiated by a reduction of serum androgens .",
    "target_text": "Androgen receptor blockade might be potentiated by a reduction of serum androgens ."
  },
  {
    "input_text": "Flutamide affects androgen receptor behavior during the menstrual cycle .",
    "target_text": "Flutamide affects <protein> androgen receptor </protein> behavior during the menstrual cycle ."
  },
  {
    "input_text": "The meaning of this finding remains to be elucidated .",
    "target_text": "The meaning of this finding remains to be elucidated ."
  },
  {
    "input_text": "Constitutive expression of HIV-1 tat protein in human Jurkat T cells using a BK virus vector .",
    "target_text": "Constitutive expression of <protein> HIV-1 tat protein </protein> in <cell_line> human <cell_line> Jurkat T cells </cell_line> </cell_line> using a BK virus vector ."
  },
  {
    "input_text": "The production and characterization of Jurkat cell lines that constitutively express functional human immune deficiency virus type 1 ( HIV-1 ) tat protein , using a BK virus plasmid expression vector and HIV-1 tat cDNA , is described .",
    "target_text": "The production and characterization of <cell_line> Jurkat cell lines </cell_line> that constitutively express functional <protein> human immune deficiency virus type 1 ( HIV-1 ) <protein> tat protein </protein> </protein> , using a BK virus plasmid expression vector and <DNA> HIV-1 tat cDNA </DNA> , is described ."
  },
  {
    "input_text": "An increased growth rate of these Jurkat-tat cell lines as compared with control cell lines was observed .",
    "target_text": "An increased growth rate of these <cell_line> Jurkat-tat cell lines </cell_line> as compared with <cell_line> control cell lines </cell_line> was observed ."
  },
  {
    "input_text": "A PEBP2 alpha/AML-1-related factor increases osteocalcin promoter activity through its binding to an osteoblast-specific cis-acting element .",
    "target_text": "A <protein> PEBP2 alpha/AML-1-related factor </protein> increases <DNA> osteocalcin promoter </DNA> activity through its binding to an <DNA> osteoblast-specific cis-acting element </DNA> ."
  },
  {
    "input_text": "To identify osteoblast-specific cis-acting elements and trans-acting factors , we initiated an analysis of the promoter of a mouse osteocalcin gene , an osteoblast-specific gene .",
    "target_text": "To identify <DNA> osteoblast-specific cis-acting elements </DNA> and <protein> trans-acting factors </protein> , we initiated an analysis of the <DNA> promoter </DNA> of a <DNA> mouse osteocalcin gene </DNA> , an <DNA> osteoblast-specific gene </DNA> ."
  },
  {
    "input_text": "In this promoter , we identified two osteoblast-specific cis-acting elements ( Ducy , P. and Karsenty , G. ( 1995 ) Mol.Cell.Biol.15 , 1858-1869 ) .",
    "target_text": "In this promoter , we identified two <DNA> osteoblast-specific cis-acting elements </DNA> ( Ducy , P. and Karsenty , G. ( 1995 ) Mol.Cell.Biol.15 , 1858-1869 ) ."
  },
  {
    "input_text": "The sequence of one of these elements , OSE2 , is identical to the DNA-binding site of the PEBP2 alpha/AML-1 transcription factors , the mammalian homologues of the Drosophila Runt protein .",
    "target_text": "The sequence of one of these <DNA> elements </DNA> , <DNA> OSE2 </DNA> , is identical to the <DNA> DNA-binding site </DNA> of the <protein> PEBP2 alpha/AML-1 transcription factors </protein> , the <protein> mammalian homologues </protein> of the <protein> Drosophila Runt protein </protein> ."
  },
  {
    "input_text": "Here we show , using nuclear extracts , recombinant protein , and a specific antiserum against AML-1 proteins in DNA-binding assays , that one member of this family , AML-1B , binds specifically to OSE2 and is immunologically related to OSF2 , the factor present in osteoblast nuclear extracts that binds to OSE2 .",
    "target_text": "Here we show , using nuclear extracts , <protein> recombinant protein </protein> , and a specific antiserum against <protein> AML-1 proteins </protein> in DNA-binding assays , that one member of this family , <protein> AML-1B </protein> , binds specifically to <DNA> OSE2 </DNA> and is immunologically related to <protein> OSF2 </protein> , the factor present in osteoblast nuclear extracts that binds to <DNA> OSE2 </DNA> ."
  },
  {
    "input_text": "By DNA cotransfection experiments , we also demonstrate that AML-1B can increase the activity of a short osteocalcin promoter through its binding to OSE2 .",
    "target_text": "By DNA cotransfection experiments , we also demonstrate that <protein> AML-1B </protein> can increase the activity of a short <DNA> osteocalcin promoter </DNA> through its binding to <DNA> OSE2 </DNA> ."
  },
  {
    "input_text": "Lastly , the different mobilities of osteoblast nuclear extract-DNA complexes compared with T-cell nuclear extract-DNA complexes , along with the inability of OSF2 to be upregulated by retinoic acid , unlike the other PEBP2 alpha factors , suggest that OSF2 is a new member of this family of transcription factors .",
    "target_text": "Lastly , the different mobilities of <protein> osteoblast nuclear extract-DNA complexes </protein> compared with <protein> T-cell nuclear extract-DNA complexes </protein> , along with the inability of <protein> OSF2 </protein> to be upregulated by retinoic acid , unlike the other <protein> PEBP2 alpha factors </protein> , suggest that <protein> OSF2 </protein> is a new member of this family of <protein> transcription factors </protein> ."
  },
  {
    "input_text": "Thus , this study demonstrates that AML-1B can increase gene expression of an osteoblast-specific gene through its binding to an osteoblast-specific cis-acting element and presents evidence that OSF2 is a member of the PEBP2 alpha/AML-1 family of transcription factors .",
    "target_text": "Thus , this study demonstrates that <protein> AML-1B </protein> can increase gene expression of an <DNA> osteoblast-specific gene </DNA> through its binding to an <DNA> osteoblast-specific cis-acting element </DNA> and presents evidence that <protein> OSF2 </protein> is a member of the <protein> PEBP2 alpha/AML-1 family </protein> of <protein> transcription factors </protein> ."
  },
  {
    "input_text": "Initiation binding repressor , a factor that binds to the transcription initiation site of the histone h5 gene , is a glycosylated member of a family of cell growth regulators [ corrected ] [ published erratum appears in Mol Cell Biol 1996 Feb ; 16 ( 2 ) : 735 ]",
    "target_text": "<protein> Initiation binding repressor </protein> , a factor that binds to the <DNA> transcription initiation site </DNA> of the <DNA> <protein> histone h5 </protein> gene </DNA> , is a <protein> glycosylated member </protein> of a family of <protein> cell growth regulators </protein> [ corrected ] [ published erratum appears in Mol Cell Biol 1996 Feb ; 16 ( 2 ) : 735 ]"
  },
  {
    "input_text": "Initiation binding repressor [ corrected ] ( IBR ) is a chicken erythrocyte factor ( apparent molecular mass , 70 to 73 kDa ) that binds to the sequences spanning the transcription initiation site of the histone h5 gene , repressing its transcription .",
    "target_text": "<protein> Initiation binding repressor </protein> [ corrected ] ( <protein> IBR </protein> ) is a <protein> chicken erythrocyte factor </protein> ( apparent molecular mass , 70 to 73 kDa ) that binds to the sequences spanning the <DNA> transcription initiation site </DNA> of the <DNA> <protein> histone h5 </protein> gene </DNA> , repressing its transcription ."
  },
  {
    "input_text": "A variety of other cells , including transformed erythroid precursors , do not have IBR but a factor referred to as IBF ( 68 to 70 kDa ) that recognizes the same IBR sites .",
    "target_text": "A variety of other cells , including <cell_type> transformed erythroid precursors </cell_type> , do not have <protein> IBR </protein> but a factor referred to as <protein> IBF </protein> ( 68 to 70 kDa ) that recognizes the same <protein> IBR </protein> sites ."
  },
  {
    "input_text": "We have cloned the IBR cDNA and studied the relationship of IBR and IBF .",
    "target_text": "We have cloned the <DNA> <protein> IBR </protein> cDNA </DNA> and studied the relationship of <protein> IBR </protein> and <protein> IBF </protein> ."
  },
  {
    "input_text": "IBR is a 503-amino-acid-long acidic protein which is 99.0 % identical to the recently reported human NRF-1/alpha-Pal factor and highly related to the invertebrate transcription factors P3A2 and erected wing gene product ( EWG ) .",
    "target_text": "<protein> IBR </protein> is a <protein> 503-amino-acid-long acidic protein </protein> which is 99.0 % identical to the recently reported <protein> human NRF-1/alpha-Pal factor </protein> and highly related to the invertebrate <protein> transcription factors </protein> <protein> P3A2 </protein> and <protein> erected wing gene product </protein> ( <protein> EWG </protein> ) ."
  },
  {
    "input_text": "We present evidence that IBR and IBF are most likely identical proteins , differing in their degree of glycosylation .",
    "target_text": "We present evidence that <protein> IBR </protein> and <protein> IBF </protein> are most likely identical proteins , differing in their degree of glycosylation ."
  },
  {
    "input_text": "We have analyzed several molecular aspects of IBR/F and shown that the factor associates as stable homodimers and that the dimer is the relevant DNA-binding species .",
    "target_text": "We have analyzed several molecular aspects of <protein> IBR/F </protein> and shown that the factor associates as stable <protein> homodimers </protein> and that the <protein> dimer </protein> is the <protein> relevant DNA-binding species </protein> ."
  },
  {
    "input_text": "The evolutionarily conserved N-terminal half of IBR/F harbors the DNA-binding/dimerization domain ( outer limits , 127 to 283 ) , one or several casein kinase II sites ( 37 to 67 ) , and a bipartite nuclear localization signal ( 89 to 106 ) which appears to be necessary for nuclear targeting .",
    "target_text": "The evolutionarily conserved <protein> N-terminal half </protein> of <protein> IBR/F </protein> harbors the <protein> DNA-binding/dimerization domain </protein> ( outer limits , 127 to 283 ) , one or several <protein> casein kinase II sites </protein> ( 37 to 67 ) , and a <protein> bipartite nuclear localization signal </protein> ( 89 to 106 ) which appears to be necessary for nuclear targeting ."
  },
  {
    "input_text": "Binding site selection revealed that the alternating RCGCRYGCGY consensus constitutes high-affinity IBR/F binding sites and that the direct-repeat palindrome TGCGCATGCGCA is the optimal site .",
    "target_text": "Binding site selection revealed that the <protein> alternating RCGCRYGCGY consensus </protein> constitutes high-affinity <DNA> <protein> IBR/F </protein> binding sites </DNA> and that the <DNA> direct-repeat palindrome </DNA> TGCGCATGCGCA is the <DNA> optimal site </DNA> ."
  },
  {
    "input_text": "A survey of genes potentially regulated by this family of factors primarily revealed genes involved in growth-related metabolism .",
    "target_text": "A survey of <DNA> genes </DNA> potentially regulated by this family of <protein> factors </protein> primarily revealed <DNA> genes </DNA> involved in growth-related metabolism ."
  },
  {
    "input_text": "Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1 , NF kappa B , and Sp1 transcription factors .",
    "target_text": "Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between <protein> interferon regulatory factor-1 </protein> , <protein> NF kappa B </protein> , and <protein> Sp1 </protein> <protein> transcription factors </protein> ."
  },
  {
    "input_text": "We investigated the molecular basis of the synergistic induction by interferon-gamma ( IFN-gamma ) / tumor necrosis factor-alpha ( TNF-alpha ) of human interleukin-6 ( IL-6 ) gene in THP-1 monocytic cells , and compared it with the basis of this induction by lipopolysaccharide ( LPS ) .",
    "target_text": "We investigated the molecular basis of the synergistic induction by <protein> interferon-gamma </protein> ( <protein> IFN-gamma </protein> ) / <protein> tumor necrosis factor-alpha </protein> ( <protein> TNF-alpha </protein> ) of <DNA> human interleukin-6 ( IL-6 ) gene </DNA> in <cell_type> THP-1 monocytic cells </cell_type> , and compared it with the basis of this induction by lipopolysaccharide ( LPS ) ."
  },
  {
    "input_text": "Functional studies with IL-6 promoter demonstrated that three regions are the targets of the IFN-gamma and/or TNF-alpha action , whereas only one of these regions seemed to be implicated in LPS activation .",
    "target_text": "Functional studies with <DNA> IL-6 promoter </DNA> demonstrated that three regions are the targets of the <protein> IFN-gamma </protein> and/or <protein> TNF-alpha </protein> action , whereas only one of these regions seemed to be implicated in LPS activation ."
  },
  {
    "input_text": "The three regions concerned are : 1 ) a region between -73 and -36 , which is the minimal element inducible by LPS or TNF-alpha ; 2 ) an element located between -181 and -73 , which appeared to regulate the response to IFN-gamma and TNF-alpha negatively ; and 3 ) a distal element upstream of -224 , which was inducible by IFN-gamma alone .",
    "target_text": "The three regions concerned are : 1 ) a region between -73 and -36 , which is the <DNA> minimal element </DNA> inducible by LPS or <protein> TNF-alpha </protein> ; 2 ) an element located between -181 and -73 , which appeared to regulate the response to <protein> IFN-gamma </protein> and <protein> TNF-alpha </protein> negatively ; and 3 ) a <DNA> distal element upstream </DNA> of -224 , which was inducible by <protein> IFN-gamma </protein> alone ."
  },
  {
    "input_text": "LPS signaling was found to involve NF kappa B activation by the p50 /p65 heterodimers .",
    "target_text": "LPS signaling was found to involve <protein> NF kappa B </protein> activation by the <protein> p50 /p65 heterodimers </protein> ."
  },
  {
    "input_text": "Synergistic induction of the IL-6 gene by IFN-gamma and TNF-alpha , in monocytic cells , involved cooperation between the IRF-1 and NF kappa B p65 homodimers with concomitant removal of the negative effect of the retinoblastoma control element present in the IL-6 promoter .",
    "target_text": "Synergistic induction of the <DNA> <protein> IL-6 </protein> gene </DNA> by <protein> IFN-gamma </protein> and <protein> TNF-alpha </protein> , in <cell_type> monocytic cells </cell_type> , involved cooperation between the <protein> IRF-1 </protein> and <protein> <protein> NF kappa B </protein> <protein> p65 </protein> homodimers </protein> with concomitant removal of the negative effect of the <DNA> retinoblastoma control element </DNA> present in the <DNA> IL-6 promoter </DNA> ."
  },
  {
    "input_text": "This removal occurred by activation of the constitutive Sp1 factor , whose increased binding activity and phosphorylation were mediated by IFN-gamma .",
    "target_text": "This removal occurred by activation of the <protein> constitutive <protein> Sp1 </protein> factor </protein> , whose increased binding activity and phosphorylation were mediated by <protein> IFN-gamma </protein> ."
  },
  {
    "input_text": "Mutation of Jak3 in a patient with SCID : essential role of Jak3 in lymphoid development .",
    "target_text": "Mutation of <protein> Jak3 </protein> in a patient with SCID : essential role of <protein> Jak3 </protein> in lymphoid development ."
  },
  {
    "input_text": "Males with X-linked severe combined immunodeficiency ( XSCID ) have defects in the common cytokine receptor gamma chain ( gamma c ) gene that encodes a shared , essential component of the receptors of interleukin-2 ( IL-2 ) , IL-4 , IL-7 , IL-9 , and IL-15 .",
    "target_text": "Males with X-linked severe combined immunodeficiency ( XSCID ) have defects in the common <DNA> <protein> cytokine receptor gamma chain </protein> ( <protein> gamma c </protein> ) gene </DNA> that encodes a shared , essential component of the receptors of <protein> interleukin-2 </protein> ( <protein> IL-2 </protein> ) , <protein> IL-4 </protein> , <protein> IL-7 </protein> , <protein> IL-9 </protein> , and <protein> IL-15 </protein> ."
  },
  {
    "input_text": "The Janus family tyrosine kinase Jak3 is the only signaling molecule known to be associated with gamma c , so it was hypothesized that defects in Jak3 might cause an XSCID -like phenotype .",
    "target_text": "The <protein> Janus family tyrosine kinase </protein> <protein> Jak3 </protein> is the only signaling molecule known to be associated with <protein> gamma c </protein> , so it was hypothesized that defects in <protein> Jak3 </protein> might cause an XSCID -like phenotype ."
  },
  {
    "input_text": "A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis .",
    "target_text": "A girl with immunological features indistinguishable from those of XSCID was therefore selected for analysis ."
  },
  {
    "input_text": "An Epstein-Barr virus ( EBV ) -transformed cell line derived from her lymphocytes had normal gamma c expression but lacked Jak3 protein and had greatly diminished Jak3 messenger RNA .",
    "target_text": "An <cell_line> Epstein-Barr virus ( EBV ) -transformed cell line </cell_line> derived from her <cell_type> lymphocytes </cell_type> had normal <protein> gamma c </protein> expression but lacked <protein> <protein> Jak3 </protein> protein </protein> and had greatly diminished <RNA> <protein> Jak3 </protein> messenger RNA </RNA> ."
  },
  {
    "input_text": "Sequencing revealed a different mutation on each allele : a single nucleotide insertion resulting in a frame shift and premature termination in the Jak3 JH4 domain and a nonsense mutation in the Jak3 JH2 domain .",
    "target_text": "Sequencing revealed a different mutation on each allele : a single nucleotide insertion resulting in a frame shift and premature termination in the <protein> <protein> Jak3 </protein> JH4 domain </protein> and a nonsense mutation in the <protein> Jak3 </protein> JH2 domain ."
  },
  {
    "input_text": "The lack of Jak3 expression correlated with impaired B cell signaling , as demonstrated by the inability of IL-4 to activate Stat6 in the EBV -transformed cell line from the patient . These observations indicate that the functions of gamma c are dependent on Jak3 and that Jak3 is essential for lymphoid development and signaling .",
    "target_text": "The lack of <protein> Jak3 </protein> expression correlated with impaired B cell signaling , as demonstrated by the inability of <protein> IL-4 </protein> to activate <protein> Stat6 </protein> in the <cell_line> EBV -transformed cell line </cell_line> from the patient . These observations indicate that the functions of <protein> gamma c </protein> are dependent on <protein> Jak3 </protein> and that <protein> Jak3 </protein> is essential for lymphoid development and signaling ."
  },
  {
    "input_text": "Constitutive overexpression of the L-selectin gene in fresh leukemic cells of adult T-cell leukemia that can be transactivated by human T-cell lymphotropic virus type 1 Tax .",
    "target_text": "Constitutive overexpression of the <DNA> <protein> L-selectin </protein> gene </DNA> in fresh <cell_type> leukemic cells </cell_type> of adult T-cell leukemia that can be transactivated by <protein> human T-cell lymphotropic virus type 1 Tax </protein> ."
  },
  {
    "input_text": "L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium .",
    "target_text": "<protein> L-selectin </protein> is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium ."
  },
  {
    "input_text": "Upon cellular activation , expression of the L-selectin gene is downregulated at both the protein and mRNA levels .",
    "target_text": "Upon cellular activation , expression of the <DNA> <protein> L-selectin </protein> gene </DNA> is downregulated at both the protein and mRNA levels ."
  },
  {
    "input_text": "To understand the mechanism of leukemic cell infiltration into organs , we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia ( ATL ) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 ( HTLV-1 ) Tax , which is a viral transcriptional transactivator .",
    "target_text": "To understand the mechanism of <cell_type> leukemic cell </cell_type> infiltration into organs , we studied the expression and regulation of <RNA> <protein> L-selectin </protein> mRNA </RNA> in fresh <cell_type> leukemic cells </cell_type> of adult T-cell leukemia ( ATL ) patients and investigated the response of the <DNA> <protein> L-selectin </protein> promoter </DNA> to <protein> human T-cell lymphotropic virus type 1 ( HTLV-1 ) Tax </protein> , which is a <protein> viral transcriptional transactivator </protein> ."
  },
  {
    "input_text": "Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens .",
    "target_text": "Flow cytometry showed that <protein> L-selectin </protein> was expressed on fresh <cell_line> ATL cells </cell_line> along with other <protein> activation antigens </protein> ."
  },
  {
    "input_text": "Northern blot analysis showed that ATL cells overexpressed that L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation .",
    "target_text": "Northern blot analysis showed that <cell_line> ATL cells </cell_line> overexpressed that <RNA> <protein> L-selectin </protein> mRNA </RNA> and that the level was aberrantly upregulated after PMA stimulation ."
  },
  {
    "input_text": "Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients .",
    "target_text": "Studies using in situ hybridization showed expression of the <RNA> <protein> L-selectin </protein> mRNA </RNA> in the infiltrating <cell_type> leukemic cells </cell_type> in the liver of two ATL patients ."
  },
  {
    "input_text": "Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration .",
    "target_text": "Intravenous injection of a <cell_line> rat T-cell line </cell_line> that overexpresses <protein> L-selectin </protein> showed increased organ infiltration ."
  },
  {
    "input_text": "The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level .",
    "target_text": "The induction of <protein> Tax </protein> expression in <cell_line> JPX9 cells </cell_line> resulted in about a twofold increase in the <RNA> mRNA </RNA> expression levels compared with the basal level ."
  },
  {
    "input_text": "Chloramphenicol acetyltransferase ( CAT ) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax .",
    "target_text": "<protein> Chloramphenicol acetyltransferase </protein> ( <protein> CAT </protein> ) assay after transient cotransfection showed about a fivefold transactivation of the <DNA> L-selectin promoter </DNA> by <protein> Tax </protein> ."
  },
  {
    "input_text": "The serum level of the shed form of L-selectin was significantly increased in ATL patients ( mean +/- SD , 4,215.4 +/- 4,111 ng/mL ) compared with those of asymptomatic carriers and healthy blood donors ( mean +/- SD , 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL , respectively ) .",
    "target_text": "The serum level of the shed form of <protein> L-selectin </protein> was significantly increased in ATL patients ( mean +/- SD , 4,215.4 +/- 4,111 ng/mL ) compared with those of asymptomatic carriers and healthy blood donors ( mean +/- SD , 1,148.0 +/- 269.0 ng/mL and 991.9 +/- 224 ng/mL , respectively ) ."
  },
  {
    "input_text": "These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax .",
    "target_text": "These results indicated that <cell_line> ATL cells </cell_line> constitutively overexpress the <DNA> <protein> L-selectin </protein> gene </DNA> that can be transactivated by HTLV-1 <protein> Tax </protein> ."
  },
  {
    "input_text": "The overexpression of L-selectin , as well as of inflammatory cytokines , by ATL cells may provide a basis for ATL cells to attach the vascular endothelium , leading to transmigration and organ infitration .",
    "target_text": "The overexpression of <protein> L-selectin </protein> , as well as of <protein> inflammatory cytokines </protein> , by <cell_line> ATL cells </cell_line> may provide a basis for <cell_line> ATL cells </cell_line> to attach the vascular endothelium , leading to transmigration and organ infitration ."
  },
  {
    "input_text": "Human herpesvirus 6 variant A , but not variant B , infects EBV -positive B lymphoid cells , activating the latent EBV genome through a BZLF-1 -dependent mechanism .",
    "target_text": "Human herpesvirus 6 variant A , but not variant B , infects <cell_line> EBV -positive B lymphoid cells </cell_line> , activating the <DNA> latent EBV genome </DNA> through a <protein> BZLF-1 </protein> -dependent mechanism ."
  },
  {
    "input_text": "Human herpesvirus 6 , a predominantly T lymphotropic virus , has been recently shown to infect some EBV -positive B cell lines , and to induce in them the activation of the EBV lytic cycle .",
    "target_text": "Human herpesvirus 6 , a predominantly T lymphotropic virus , has been recently shown to infect some <cell_line> EBV -positive B cell lines </cell_line> , and to induce in them the activation of the EBV lytic cycle ."
  },
  {
    "input_text": "Here we have confirmed and extended such observations , showing that ( 1 ) this phenomenon is restricted to the variant A of HHV-6 : in fact two isolates belonging to the HHV-6 variant B ( BA92 and Z29 ) were neither able to infect any B cell line , independently of the EBV status , nor to induce the EBV genome expression .",
    "target_text": "Here we have confirmed and extended such observations , showing that ( 1 ) this phenomenon is restricted to the variant A of HHV-6 : in fact two isolates belonging to the HHV-6 variant B ( BA92 and Z29 ) were neither able to infect any <cell_line> B cell line </cell_line> , independently of the EBV status , nor to induce the EBV genome expression ."
  },
  {
    "input_text": "The only exception is represented by the P3HR1 cells , in which , however , the infection by the variant B does not determine induction of EBV antigens ; ( 2 ) the presence of the EBV genome contributes to the susceptibility of the B cell lines to HHV-6 infection , increasing the binding sites and the percentage of infectable cells , as detected by immunoelectron microscopy ; and ( 3 ) HHV-6 infected T cells , transfected with plasmids bearing the promoter regions of the EBV early genes BZLF1 and BMRF1 , show a strong transactivation of these promoters .",
    "target_text": "The only exception is represented by the <cell_line> P3HR1 cells </cell_line> , in which , however , the infection by the variant B does not determine induction of <protein> EBV antigens </protein> ; ( 2 ) the presence of the <DNA> EBV genome </DNA> contributes to the susceptibility of the <cell_line> B cell lines </cell_line> to HHV-6 infection , increasing the binding sites and the percentage of <cell_type> infectable cells </cell_type> , as detected by immunoelectron microscopy ; and ( 3 ) <cell_line> HHV-6 infected T cells </cell_line> , transfected with <DNA> plasmids </DNA> bearing the <DNA> promoter regions </DNA> of the EBV early genes <DNA> BZLF1 </DNA> and <DNA> BMRF1 </DNA> , show a strong transactivation of these <DNA> promoters </DNA> ."
  },
  {
    "input_text": "Evidence for normal vitamin D receptor messenger ribonucleic acid and genotype in absorptive hypercalciuria .",
    "target_text": "Evidence for normal <RNA> <protein> vitamin D receptor </protein> messenger ribonucleic acid </RNA> and genotype in absorptive hypercalciuria ."
  },
  {
    "input_text": "Absorptive hypercalciuria ( a stone-forming condition ) is characterized by gut hyperabsorption of calcium , hypercalciuria , and reduced bone density .",
    "target_text": "Absorptive hypercalciuria ( a stone-forming condition ) is characterized by gut hyperabsorption of calcium , hypercalciuria , and reduced bone density ."
  },
  {
    "input_text": "Inasmuch as these features implicate enhanced calcitriol action in gut and bone , we analyzed the vitamin D receptor ( VDR ) gene to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium .",
    "target_text": "Inasmuch as these features implicate enhanced calcitriol action in gut and bone , we analyzed the <DNA> <protein> vitamin D receptor </protein> ( <protein> VDR </protein> ) gene </DNA> to ascertain whether an abnormality of this gene marks patients with intestinal hyperabsorption of calcium ."
  },
  {
    "input_text": "We have compared the frequency of a restriction fragment length polymorphism ( Bsm I ) associated with different alleles of the VDR gene in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects .",
    "target_text": "We have compared the frequency of a <DNA> restriction fragment length polymorphism </DNA> ( <DNA> Bsm I </DNA> ) associated with different alleles of the <DNA> <protein> VDR </protein> gene </DNA> in a group of 33 well characterized absorptive hypercalciuric patients and a group of 36 normal race- and age-matched control subjects ."
  },
  {
    "input_text": "There was no difference between the distribution of the VDR alleles in the patient population when compared with the normal population .",
    "target_text": "There was no difference between the distribution of the <protein> VDR </protein> alleles in the patient population when compared with the normal population ."
  },
  {
    "input_text": "The coding region of VDR messenger RNA was also normal , as determined by both DNA sequence analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients .",
    "target_text": "The coding region of <RNA> <protein> VDR </protein> messenger RNA </RNA> was also normal , as determined by both <DNA> DNA sequence </DNA> analysis and chemical mismatch cleavage analysis of copy DNA from 11 index absorptive hypercalciuric patients ."
  },
  {
    "input_text": "On the basis of these results , we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the VDR and are not linked to a common VDR genotype .",
    "target_text": "On the basis of these results , we propose that the enhanced intestinal calcium absorption invariably seen in absorptive hypercalciuria and attendant symptoms of this disorder are not attributable to mutations of the <protein> VDR </protein> and are not linked to a common <DNA> <protein> VDR </protein> genotype </DNA> ."
  },
  {
    "input_text": "Transcriptional regulation of the gene encoding the human C-type lectin leukocyte receptor AIM/CD69 and functional characterization of its tumor necrosis factor-alpha -responsive elements .",
    "target_text": "Transcriptional regulation of the gene encoding the <protein> human C-type lectin leukocyte receptor </protein> <protein> AIM/CD69 </protein> and functional characterization of its <DNA> <protein> tumor necrosis factor-alpha </protein> -responsive <DNA> elements </DNA> </DNA> ."
  },
  {
    "input_text": "The human activation antigen CD69 is a member of the C-type animal lectin superfamily that functions as a signal-transmitting receptor .",
    "target_text": "The <protein> human activation antigen </protein> <protein> CD69 </protein> is a member of the <protein> C-type animal lectin superfamily </protein> that functions as a <protein> signal-transmitting receptor </protein> ."
  },
  {
    "input_text": "Although the expression of CD69 can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli , in vivo it is mainly expressed by T- lymphocytes located in the inflammatory infiltrates of several human diseases .",
    "target_text": "Although the expression of <protein> CD69 </protein> can be induced in vitro on cells of most hematopoietic lineages with a wide variety of stimuli , in vivo it is mainly expressed by <cell_type> T- <cell_type> lymphocytes </cell_type> </cell_type> located in the inflammatory infiltrates of several human diseases ."
  },
  {
    "input_text": "To elucidate the mechanisms that regulate the constitutive and inducible expression of CD69 by leukocytes , we isolated the promoter region of the CD69 gene and carried out its functional characterization .",
    "target_text": "To elucidate the mechanisms that regulate the constitutive and inducible expression of <protein> CD69 </protein> by <cell_type> leukocytes </cell_type> , we isolated the <DNA> promoter region </DNA> of the <protein> CD69 </protein> gene and carried out its functional characterization ."
  },
  {
    "input_text": "Sequence analysis of the 5'-flanking region of the CD69 gene revealed the presence of a potential TATA element 30 base pairs upstream of the major transcription initiation site and several putative binding sequences for inducible transcription factors ( NF-kappa B , Egr-1 , AP-1 ) , which might mediate the inducible expression of this gene .",
    "target_text": "Sequence analysis of the <DNA> 5'-flanking region </DNA> of the <DNA> <protein> CD69 </protein> gene </DNA> revealed the presence of a potential <DNA> TATA element </DNA> <DNA> 30 base pairs upstream </DNA> of the major <DNA> transcription initiation site </DNA> and several putative binding sequences for inducible <protein> transcription factors </protein> ( <protein> NF-kappa B </protein> , <protein> Egr-1 </protein> , <protein> AP-1 </protein> ) , which might mediate the inducible expression of this gene ."
  },
  {
    "input_text": "Transient expression of CD69 promoter-based reporter gene constructs in K562 cells indicated that the proximal promoter region spanning positions -78 to +16 contained the cis-acting sequences necessary for basal and phorbol 12-myristate 13-acetate -inducible transcription of the CD69 gene .",
    "target_text": "Transient expression of <DNA> <protein> CD69 </protein> promoter-based reporter gene constructs </DNA> in <cell_line> K562 cells </cell_line> indicated that the <DNA> proximal <DNA> promoter region </DNA> </DNA> spanning positions -78 to +16 contained the <DNA> cis-acting sequences </DNA> necessary for basal and phorbol 12-myristate 13-acetate -inducible transcription of the <DNA> <protein> CD69 </protein> gene </DNA> ."
  },
  {
    "input_text": "Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate .",
    "target_text": "Removal of the upstream sequences located between positions -78 and -38 resulted in decreased promoter strength and abolished the response to phorbol 12-myristate 13-acetate ."
  },
  {
    "input_text": "We also found that tumor necrosis factor-alpha ( TNF-alpha ) is capable of inducing the surface expression of the CD69 molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the CD69 gene , suggesting that this cytokine may regulate in vivo the expression of CD69 .",
    "target_text": "We also found that <protein> tumor necrosis factor-alpha </protein> ( <protein> TNF-alpha </protein> ) is capable of inducing the surface expression of the <protein> CD69 </protein> molecule as well as the promoter activity of fusion plasmids that contain 5'-flanking sequences of the <protein> CD69 </protein> gene , suggesting that this cytokine may regulate in vivo the expression of <protein> CD69 </protein> ."
  },
  {
    "input_text": "( ABSTRACT TRUNCATED AT 250 WORDS )",
    "target_text": "( ABSTRACT TRUNCATED AT 250 WORDS )"
  },
  {
    "input_text": "Characterization of 5' end of human thromboxane receptor gene .",
    "target_text": "Characterization of <DNA> 5' end of <DNA> human thromboxane receptor gene </DNA> </DNA> ."
  },
  {
    "input_text": "Organizational analysis and mapping of protein kinase C -- responsive elements regulating expression in platelets .",
    "target_text": "Organizational analysis and mapping of <DNA> protein kinase C -- responsive <DNA> elements </DNA> </DNA> regulating expression in <cell_type> platelets </cell_type> ."
  },
  {
    "input_text": "Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction .",
    "target_text": "<protein> <cell_type> Platelet </cell_type> thromboxane receptors </protein> are acutely and reversibly upregulated after acute myocardial infarction ."
  },
  {
    "input_text": "To determine if platelet thromboxane receptors are under transcriptional control , we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene .",
    "target_text": "To determine if platelet <protein> thromboxane receptors </protein> are under transcriptional control , we isolated and characterized <DNA> human genomic DNA clones </DNA> containing the <DNA> 5' flanking region </DNA> of the <DNA> thromboxane receptor gene </DNA> ."
  },
  {
    "input_text": "The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA .",
    "target_text": "The <DNA> exon-intron structure </DNA> of the <DNA> 5' portion </DNA> of the <DNA> <protein> thromboxane receptor </protein> gene </DNA> was determined initially by comparing the <DNA> nucleotide sequence </DNA> of the <DNA> 5' flanking genomic clone </DNA> with that of a <DNA> novel human uterine <protein> thromboxane receptor </protein> cDNA </DNA> that extended the <RNA> mRNA </RNA> <DNA> 141 bp further upstream </DNA> than the <DNA> previously identified human placental cDNA </DNA> ."
  },
  {
    "input_text": "A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site .",
    "target_text": "A major <DNA> transcription initiation site </DNA> was located in three human tissues approximately <DNA> 560 bp upstream </DNA> from the <DNA> translation initiation codon </DNA> and <DNA> 380 bp upstream </DNA> from any previously identified <DNA> transcription initiation site </DNA> ."
  },
  {
    "input_text": "The thromboxane receptor gene has neither a TATA nor a CAAT consensus site .",
    "target_text": "The <DNA> <protein> thromboxane receptor </protein> gene </DNA> has neither a <DNA> TATA </DNA> nor a <DNA> CAAT consensus site </DNA> ."
  },
  {
    "input_text": "Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/ chloramphenicol acetyltransferase ( CAT ) chimera plasmids into platelet-like K562 cells .",
    "target_text": "Promoter function of the <DNA> 5' flanking region </DNA> of the <DNA> <protein> thromboxane receptor </protein> gene </DNA> was evaluated by transfection of <DNA> <DNA> <protein> thromboxane receptor </protein> gene </DNA> promoter/ <protein> chloramphenicol acetyltransferase </protein> ( <protein> CAT </protein> ) chimera plasmids </DNA> into platelet-like <cell_line> K562 cells </cell_line> ."
  },
  {
    "input_text": "Thromboxane receptor promoter activity , as assessed by CAT expression , was relatively weak but was significantly enhanced by phorbol ester treatment .",
    "target_text": "Thromboxane <DNA> receptor promoter </DNA> activity , as assessed by <protein> CAT </protein> expression , was relatively weak but was significantly enhanced by phorbol ester treatment ."
  },
  {
    "input_text": "Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester -responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 ( AP-2 ) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site .",
    "target_text": "Functional analysis of <DNA> 5' deletion constructs </DNA> in transfected <cell_line> K562 cells </cell_line> and gel mobility shift localized the major phorbol ester -responsive motifs in the <DNA> <protein> thromboxane receptor </protein> gene </DNA> promoter to a cluster of <DNA> <protein> activator protein-2 </protein> ( <protein> AP-2 </protein> ) binding consensus sites </DNA> located approximately 1.8 kb 5' from the <DNA> transcription initiation site </DNA> ."
  },
  {
    "input_text": "These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2 -like nuclear factor binding to upstream promoter elements .",
    "target_text": "These studies are the first to determine the structure and organization of the 5' end of the <DNA> <protein> thromboxane receptor </protein> gene </DNA> and demonstrate that <DNA> <protein> thromboxane receptor </protein> gene </DNA> expression can be regulated by activation of <protein> protein kinase C </protein> via induction of an <protein> <protein> AP-2 </protein> -like nuclear factor </protein> binding to <DNA> upstream promoter elements </DNA> ."
  },
  {
    "input_text": "These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells .",
    "target_text": "These findings strongly suggest that the mechanism for previously described upregulation of <protein> platelet thromboxane receptors </protein> after acute myocardial infarction is increased <DNA> <protein> thromboxane receptor </protein> gene </DNA> transcription in <cell_type> platelet-progenitor cells </cell_type> ."
  },
  {
    "input_text": "Estrogen receptor concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients .",
    "target_text": "<protein> Estrogen receptor </protein> concentration and social factors as predictors of natural killer cell activity in early-stage breast cancer patients ."
  },
  {
    "input_text": "Confirmation of a model .",
    "target_text": "Confirmation of a model ."
  },
  {
    "input_text": "Previous work of ours has demonstrated that a significant amount of natural killer ( NK ) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor ( ER ) status of the tumor and by social factors , namely , perceived social support and seeking social support as a general coping strategy .",
    "target_text": "Previous work of ours has demonstrated that a significant amount of natural killer ( NK ) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the <protein> estrogen receptor </protein> ( <protein> ER </protein> ) status of the tumor and by social factors , namely , perceived social support and seeking social support as a general coping strategy ."
  },
  {
    "input_text": "As considerable evidence has accumulated that social support in both animal and human populations may have survival value , we sought to test the reliability of this regression model , using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients .",
    "target_text": "As considerable evidence has accumulated that social support in both animal and human populations may have survival value , we sought to test the reliability of this regression model , using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients ."
  },
  {
    "input_text": "It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration , with higher NK activity associated with ER - status .",
    "target_text": "It was found that the most significant variable predicting NK activity at follow-up was tumor <protein> ER </protein> concentration , with higher NK activity associated with <protein> ER </protein> - status ."
  },
  {
    "input_text": "In addition , seeking social support as a coping strategy , as well as the perceived quality of support , also entered the model to account for a significant amount of NK activity variance ( multivariate F = 5.25 , p less than 0.001 ) .",
    "target_text": "In addition , seeking social support as a coping strategy , as well as the perceived quality of support , also entered the model to account for a significant amount of NK activity variance ( multivariate F = 5.25 , p less than 0.001 ) ."
  },
  {
    "input_text": "If , as the literature suggests , NK activity is relevant to breast cancer control , and since ER - tumors have a worse prognosis , we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site , or because blocking factors at the site of the tumor prevent local tumor control at the site of action .",
    "target_text": "If , as the literature suggests , NK activity is relevant to breast cancer control , and since <protein> ER </protein> - tumors have a worse prognosis , we suggest here that perhaps such tumors are resistant to control by <cell_type> NK cells </cell_type> because they lack the ability to attract an accumulation of <cell_type> effector cells </cell_type> to the tumor site , or because blocking factors at the site of the tumor prevent local tumor control at the site of action ."
  },
  {
    "input_text": "The finding related to social support also replicates results from an independent sample of breast cancer patients .",
    "target_text": "The finding related to social support also replicates results from an independent sample of breast cancer patients ."
  },
  {
    "input_text": "This finding , taken together with other evidence that this social variable is associated with longer survival in breast cancer populations , underscores the potential importance of this social support variable .",
    "target_text": "This finding , taken together with other evidence that this social variable is associated with longer survival in breast cancer populations , underscores the potential importance of this social support variable ."
  },
  {
    "input_text": "Our findings also suggest one possible immunological variable involved , with potential clinical significance , for this patient population .",
    "target_text": "Our findings also suggest one possible immunological variable involved , with potential clinical significance , for this patient population ."
  },
  {
    "input_text": "Solution structure of the sequence-specific HMG box of the lymphocyte transcriptional activator Sox-4 .",
    "target_text": "Solution structure of the <DNA> sequence-specific HMG box </DNA> of the <protein> lymphocyte transcriptional activator </protein> <protein> Sox-4 </protein> ."
  },
  {
    "input_text": "Two groups of HMG box proteins are distinguished .",
    "target_text": "Two groups of <protein> HMG box proteins </protein> are distinguished ."
  },
  {
    "input_text": "Proteins in the first group contain multiple HMG boxes , are non-sequence-specific , and recognize structural features as found in cruciform DNA and cross-over DNA .",
    "target_text": "Proteins in the first group contain multiple <protein> HMG boxes </protein> , are non-sequence-specific , and recognize structural features as found in <DNA> cruciform DNA </DNA> and <DNA> cross-over DNA </DNA> ."
  },
  {
    "input_text": "The abundant chromosomal protein HMG-1 belongs to this subgroup .",
    "target_text": "The abundant <protein> chromosomal protein </protein> <protein> HMG-1 </protein> belongs to this subgroup ."
  },
  {
    "input_text": "Proteins in the second group carry a single HMG box with affinity for the minor groove of the heptamer motif AACAAAG or variations thereof .",
    "target_text": "Proteins in the second group carry a <protein> single HMG box </protein> with affinity for the <DNA> minor groove </DNA> of the <DNA> heptamer motif </DNA> AACAAAG or variations thereof ."
  },
  {
    "input_text": "A solution structure for the non-sequence-specific C-terminal HMG box of HMG-1 has recently been proposed .",
    "target_text": "A solution structure for the non-sequence-specific <protein> C-terminal HMG box </protein> of <protein> HMG-1 </protein> has recently been proposed ."
  },
  {
    "input_text": "Now , we report the solution structure of the sequence-specific HMG-box of the SRY-related protein Sox-4 .",
    "target_text": "Now , we report the solution structure of the <protein> sequence-specific HMG-box </protein> of the <protein> SRY-related protein </protein> <protein> Sox-4 </protein> ."
  },
  {
    "input_text": "NMR analysis demonstrated the presence of three alpha-helices ( Val10-Gln22 , Glu30-Leu41 and Phe50-Tyr65 ) connected by loop regions ( Ser23-Ala49 and Leu42-Pro49 ) .",
    "target_text": "NMR analysis demonstrated the presence of three <protein> alpha-helices </protein> ( <protein> Val10-Gln22 </protein> , <protein> Glu30-Leu41 </protein> and <protein> Phe50-Tyr65 </protein> ) connected by <protein> loop regions </protein> ( <protein> Ser23-Ala49 </protein> and <protein> Leu42-Pro49 </protein> ) ."
  },
  {
    "input_text": "Helices I and II are positioned in an antiparallel mode and form one arm of the HMG box .",
    "target_text": "Helices I and II are positioned in an <protein> antiparallel mode </protein> and form one arm of the <protein> HMG box </protein> ."
  },
  {
    "input_text": "Helix III is less rigid , makes an average angle of about 90 degrees with helices I and II , and constitutes the other arm of the molecule .",
    "target_text": "<protein> Helix III </protein> is less rigid , makes an average angle of about 90 degrees with helices I and II , and constitutes the other arm of the molecule ."
  },
  {
    "input_text": "As in HMG1B , the overall structure of the Sox-4 HMG box is L-shaped and is maintained by a cluster of conserved , mainly aromatic residues .",
    "target_text": "As in <protein> HMG1B </protein> , the overall structure of the <protein> Sox-4 </protein> <protein> HMG box </protein> is L-shaped and is maintained by a cluster of conserved , mainly aromatic residues ."
  },
  {
    "input_text": "Nuclear factor-IL6 activates the human IL-4 promoter in T cells .",
    "target_text": "<protein> Nuclear factor-IL6 </protein> activates the <DNA> human IL-4 promoter </DNA> in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "Positive regulatory element I ( PRE-I ) is a strong enhancer element essential for expression of the human IL-4 gene .",
    "target_text": "<DNA> Positive regulatory element I </DNA> ( <DNA> PRE-I </DNA> ) is a strong <DNA> enhancer element </DNA> essential for expression of the <DNA> human IL-4 gene </DNA> ."
  },
  {
    "input_text": "To identify transcription factors binding to PRE-I , we screened a cDNA expression library from Jurkat T cells and isolated a cDNA encoding nuclear factor ( NF ) -IL6 ( also known as C/EBP beta ) .",
    "target_text": "To identify <protein> transcription factors </protein> binding to <DNA> PRE-I </DNA> , we screened a <DNA> cDNA expression library </DNA> from <cell_line> Jurkat <cell_type> T cells </cell_type> </cell_line> and isolated a <DNA> cDNA </DNA> encoding <protein> nuclear factor </protein> <protein> ( NF ) -IL6 </protein> ( also known as <protein> C/EBP beta </protein> ) ."
  },
  {
    "input_text": "NF-IL6 mRNA was found in human Jurkat T cells and in the mouse Th2 clone D10 , but not in Th1 clone 29 .",
    "target_text": "<RNA> NF-IL6 mRNA </RNA> was found in <cell_line> human Jurkat <cell_type> T cells </cell_type> </cell_line> and in the <cell_line> mouse Th2 clone </cell_line> <cell_line> D10 </cell_line> , but not in <cell_line> Th1 clone 29 </cell_line> ."
  },
  {
    "input_text": "rNF-IL6 expressed in bacteria was shown to specifically bind to PRE-I .",
    "target_text": "<protein> rNF-IL6 </protein> expressed in bacteria was shown to specifically bind to <DNA> PRE-I </DNA> ."
  },
  {
    "input_text": "PRE-I forms multiple DNA-protein complexes with nuclear extracts from Jurkat cells .",
    "target_text": "<DNA> PRE-I </DNA> forms <protein> multiple DNA-protein complexes </protein> with nuclear extracts from <cell_line> Jurkat cells </cell_line> ."
  },
  {
    "input_text": "Some of these complexes were demonstrated to contain NF-IL6 by using anti- C/EBP beta Abs .",
    "target_text": "Some of these complexes were demonstrated to contain <protein> NF-IL6 </protein> by using <protein> anti- <protein> C/EBP beta </protein> Abs </protein> ."
  },
  {
    "input_text": "Overexpression of NF-IL6 enhanced expression of the chloramphenicol acetyl transferase reporter gene linked to the PRE-I -thymidine kinase or the human IL-4 promoter more than 10-fold in Jurkat cells .",
    "target_text": "Overexpression of <protein> NF-IL6 </protein> enhanced expression of the <DNA> <protein> chloramphenicol acetyl transferase </protein> reporter gene </DNA> linked to the <protein> <DNA> PRE-I </DNA> -thymidine kinase </protein> or the <DNA> <protein> human IL-4 </protein> promoter </DNA> more than 10-fold in <cell_line> Jurkat cells </cell_line> ."
  },
  {
    "input_text": "Promoter deletion studies revealed two additional NF-IL6 binding sites located at positions -44 to -36 ( C/EBP proximal ) and -87 to -79 ( C/EBP medial ) , respectively .",
    "target_text": "Promoter deletion studies revealed two additional <DNA> <protein> NF-IL6 </protein> binding sites </DNA> located at positions -44 to -36 ( <protein> C/EBP proximal </protein> ) and -87 to -79 ( <protein> C/EBP medial </protein> ) , respectively ."
  },
  {
    "input_text": "Our results demonstrate that NF-IL6 is involved in transcriptional activation of the human IL-4 promoter in T cells .",
    "target_text": "Our results demonstrate that <protein> NF-IL6 </protein> is involved in transcriptional activation of the <DNA> <protein> human IL-4 </protein> promoter </DNA> in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "Identification of an I kappa B alpha-associated protein kinase in a human monocytic cell line and determination of its phosphorylation sites on I kappa B alpha .",
    "target_text": "Identification of an <protein> I kappa B alpha-associated protein kinase </protein> in a <cell_line> human monocytic cell line </cell_line> and determination of its <protein> phosphorylation sites </protein> on <protein> I kappa B alpha </protein> ."
  },
  {
    "input_text": "Nuclear factor kappa B ( NF-kappa B ) is stored in the cytoplasm as an inactive form through interaction with I kappa B .",
    "target_text": "<protein> Nuclear factor kappa B </protein> ( <protein> NF-kappa B </protein> ) is stored in the cytoplasm as an inactive form through interaction with <protein> I kappa B </protein> ."
  },
  {
    "input_text": "Stimulation of cells leads to a rapid phosphorylation of I kappa B alpha , which is presumed to be important for the subsequent degradation .",
    "target_text": "Stimulation of cells leads to a rapid phosphorylation of <protein> <protein> I kappa B </protein> alpha </protein> , which is presumed to be important for the subsequent degradation ."
  },
  {
    "input_text": "We have recently reported the establishment of a lipopolysaccharide ( LPS ) -dependent cell-free activation system of NF-kappa B in association with the induction of I kappa B alpha phosphorylation .",
    "target_text": "We have recently reported the establishment of a lipopolysaccharide ( LPS ) -dependent cell-free activation system of <protein> NF-kappa B </protein> in association with the induction of <protein> <protein> I kappa B </protein> alpha </protein> phosphorylation ."
  },
  {
    "input_text": "In this study , we have identified a kinase in cell extracts from the LPS -stimulated human monocytic cell line , THP-1 , that specifically binds and phosphorylates I kappa B alpha .",
    "target_text": "In this study , we have identified a <protein> kinase </protein> in cell extracts from the <cell_line> LPS -stimulated human monocytic cell line </cell_line> , <cell_line> THP-1 </cell_line> , that specifically binds and phosphorylates <protein> I kappa B alpha </protein> ."
  },
  {
    "input_text": "LPS stimulation transiently enhanced the I kappa B alpha -bound kinase activity in THP-1 cells .",
    "target_text": "LPS stimulation transiently enhanced the <protein> <protein> I kappa B </protein> alpha </protein> <protein> -bound kinase </protein> activity in <cell_line> THP-1 cells </cell_line> ."
  },
  {
    "input_text": "Mutational analyses of I kappa B alpha and competition experiments with the synthetic peptides identified major phosphorylation sites by the bound kinase as Ser and Thr residues in the C-terminal acidic domain of I kappa B alpha .",
    "target_text": "Mutational analyses of <protein> I kappa B </protein> alpha and competition experiments with the synthetic peptides identified major <protein> phosphorylation sites </protein> by the bound <protein> kinase </protein> as Ser and Thr residues in the <protein> C-terminal acidic domain </protein> of <protein> <protein> I kappa B </protein> alpha </protein> ."
  },
  {
    "input_text": "Moreover , we show that the peptide , corresponding to the C-terminal acidic domain of I kappa B alpha , blocked the LPS -induced NF-kappa B activation as well as inducible phosphorylation of endogenous I kappa B alpha in a cell-free system using THP-1 cells .",
    "target_text": "Moreover , we show that the peptide , corresponding to the <protein> C-terminal acidic domain </protein> of <protein> <protein> I kappa B </protein> alpha </protein> , blocked the LPS -induced <protein> NF-kappa B </protein> activation as well as inducible phosphorylation of endogenous <protein> <protein> I kappa B </protein> alpha </protein> in a cell-free system using <cell_line> THP-1 cells </cell_line> ."
  },
  {
    "input_text": "These results suggested that the bound kinase is involved in the signaling pathway of LPS by inducing the phosphorylation of the C-terminal region of I kappa B alpha and subsequent dissociation of the NF-kappa B . I kappa B alpha complex .",
    "target_text": "These results suggested that the <protein> bound kinase </protein> is involved in the signaling pathway of LPS by inducing the phosphorylation of the <protein> C-terminal region </protein> of <protein> <protein> I kappa B </protein> alpha </protein> and subsequent dissociation of the <protein> NF-kappa B </protein> . <protein> <protein> I kappa B alpha </protein> complex </protein> ."
  },
  {
    "input_text": "Bik , a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins .",
    "target_text": "<protein> Bik </protein> , a novel <protein> death-inducing protein </protein> shares a distinct sequence motif with <protein> Bcl-2 family proteins </protein> and interacts with viral and <protein> cellular survival-promoting proteins </protein> ."
  },
  {
    "input_text": "The survival-promoting activity of the Bcl-2 family of proteins appears to be modulated by interactions between various cellular proteins .",
    "target_text": "The survival-promoting activity of the <protein> Bcl-2 family </protein> of proteins appears to be modulated by interactions between various <protein> cellular proteins </protein> ."
  },
  {
    "input_text": "We have identified a novel cellular protein , Bik , that interacts with the cellular survival-promoting proteins , Bcl-2 and Bcl-xL , as well as the viral survival-promoting proteins , Epstein Barr virus -BHRF1 and adenovirus E1B-19 kDa .",
    "target_text": "We have identified a novel <protein> cellular protein </protein> , <protein> Bik </protein> , that interacts with the <protein> cellular survival-promoting proteins </protein> , <protein> Bcl-2 </protein> and <protein> Bcl-xL </protein> , as well as the <protein> viral survival-promoting proteins </protein> , <protein> Epstein Barr virus -BHRF1 </protein> and <protein> adenovirus E1B-19 kDa </protein> ."
  },
  {
    "input_text": "In transient transfection assays , Bik promotes cell death in a manner similar to the death-promoting members of the Bcl-2 family , Bax and Bak .",
    "target_text": "In transient transfection assays , <protein> Bik </protein> promotes cell death in a manner similar to the <protein> death-promoting members </protein> of the <protein> <protein> Bcl-2 </protein> family </protein> , <protein> Bax </protein> and <protein> Bak </protein> ."
  },
  {
    "input_text": "This death-promoting activity of Bik can be suppressed by coexpression of Bcl-2 , Bcl-XL , EBV-BHRF1 and E1B-19 kDa proteins suggesting that Bik may be a common target for both cellular and viral anti-apoptotic proteins .",
    "target_text": "This death-promoting activity of <protein> Bik </protein> can be suppressed by coexpression of <protein> Bcl-2 </protein> , <protein> Bcl-XL </protein> , <protein> EBV-BHRF1 </protein> and <protein> E1B-19 kDa </protein> proteins suggesting that <protein> Bik </protein> may be a common target for both cellular and viral anti-apoptotic proteins ."
  },
  {
    "input_text": "While Bik does not show overt homology to the BH1 and BH2 conserved domains characteristic of the Bcl-2 family , it does share a 9 amino acid domain ( BH3 ) with Bax and Bak which may be a critical determinant for the death-promoting activity of these proteins .",
    "target_text": "While <protein> Bik </protein> does not show overt homology to the <protein> BH1 </protein> and <protein> BH2 </protein> conserved domains characteristic of the <protein> Bcl-2 family </protein> , it does share a 9 <protein> amino acid domain </protein> ( <protein> BH3 </protein> ) with <protein> Bax </protein> and <protein> Bak </protein> which may be a critical determinant for the death-promoting activity of these proteins ."
  },
  {
    "input_text": "The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes .",
    "target_text": "The <DNA> human TCF-1 gene </DNA> encodes a <protein> nuclear DNA-binding protein </protein> uniquely expressed in normal and neoplastic T-lineage lymphocytes ."
  },
  {
    "input_text": "The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers .",
    "target_text": "The <DNA> <protein> TCF-1 </protein> gene </DNA> encodes a <protein> putative transcription factor </protein> with affinity for a <DNA> sequence motif </DNA> occurring in a number of <DNA> T-cell enhancers </DNA> ."
  },
  {
    "input_text": "TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines .",
    "target_text": "<RNA> <protein> TCF-1 </protein> mRNA </RNA> was originally found to be expressed in a T cell-specific fashion within a set of <cell_line> <cell_line> human </cell_line> and <cell_line> mouse cell lines </cell_line> </cell_line> ."
  },
  {
    "input_text": "In contrast , expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis .",
    "target_text": "In contrast , expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis ."
  },
  {
    "input_text": "We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein .",
    "target_text": "We have now raised a <protein> monoclonal antibody </protein> to document expression and biochemistry of the <protein> human <protein> TCF-1 </protein> protein </protein> ."
  },
  {
    "input_text": "As expected , the TCF-1 protein was detectable only in cell lines of T lineage .",
    "target_text": "As expected , the <protein> TCF-1 protein </protein> was detectable only in <cell_line> cell lines of T lineage </cell_line> ."
  },
  {
    "input_text": "Its expression was always restricted to the nucleus .",
    "target_text": "Its expression was always restricted to the nucleus ."
  },
  {
    "input_text": "Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues .",
    "target_text": "Immunohistochemistry on a panel of human tissues revealed that the <protein> <protein> TCF-1 </protein> protein </protein> was found exclusively in thymocytes and in <cell_line> CD3+ <cell_type> T cells </cell_type> </cell_line> in peripheral lymphoid tissues ."
  },
  {
    "input_text": "Western blotting yielded a set of bands ranging from 25 kD to 55 kD , resulting from extensive alternative splicing .",
    "target_text": "Western blotting yielded a set of bands ranging from 25 kD to 55 kD , resulting from extensive alternative splicing ."
  },
  {
    "input_text": "The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation , but was absent from a large number of other hematologic neoplasms .",
    "target_text": "The <protein> TCF-1 </protein> protein was detectable in all samples of a set of 22 <cell_type> T-cell malignancies </cell_type> of various stages of maturation , but was absent from a large number of other <cell_type> hematologic neoplasms </cell_type> ."
  },
  {
    "input_text": "These observations imply a T cell-specific function for TCF-1 , a notion corroborated by recent observations on Tcf-1 knock-out mice .",
    "target_text": "These observations imply a T cell-specific function for <protein> TCF-1 </protein> , a notion corroborated by recent observations on Tcf-1 knock-out mice ."
  },
  {
    "input_text": "In addition , these results indicate that nuclear TCF-1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies .",
    "target_text": "In addition , these results indicate that nuclear <protein> TCF-1 </protein> expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies ."
  },
  {
    "input_text": "Cross-linking of Fc gamma receptors activates HIV-1 long terminal repeat -driven transcription in human monocytes .",
    "target_text": "Cross-linking of <protein> Fc gamma receptors </protein> activates <DNA> HIV-1 long terminal repeat </DNA> -driven transcription in <cell_type> human monocytes </cell_type> ."
  },
  {
    "input_text": "Elevation of the levels of circulating immune complexes frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS .",
    "target_text": "Elevation of the levels of <protein> circulating immune complexes </protein> frequently accompanies HIV-1 infection and is a prognostic indicator of clinical progression from asymptomatic infection to AIDS ."
  },
  {
    "input_text": "Here we report that cross-linking of Fc gamma RI or Fc gamma RII by adherent human IgG or by specific anti-Fc gamma R mAb activates HIV-1 gene expression in the human monocytic cell line BF24 and increased HIV RNA expression in monocytes from HIV infected patients as assayed by reverse transcription-PCR .",
    "target_text": "Here we report that cross-linking of <protein> Fc gamma RI </protein> or <protein> Fc gamma RII </protein> by <protein> adherent human IgG </protein> or by specific <protein> anti-Fc gamma R mAb </protein> activates HIV-1 gene expression in the <cell_line> human monocytic cell line </cell_line> <cell_line> BF24 </cell_line> and increased <RNA> HIV RNA </RNA> expression in <cell_type> monocytes </cell_type> from HIV infected patients as assayed by reverse transcription-PCR ."
  },
  {
    "input_text": "In THP-1 cells , Fc gamma R cross-linking induced NF-kappa B , which is known to bind to the regulatory region of the long terminal repeat ( LTR ) of HIV-1 and to activate HIV-1 transcription . Anti-TNF-alpha antibody but not anti-IL-1 beta antibody strongly inhibited both the induction of HIV-1 - LTR -driven transcription and the induction of NF-kappa B by Fc gamma R cross-linking .",
    "target_text": "In <cell_line> <cell_line> THP-1 </cell_line> cells </cell_line> , <protein> Fc gamma R </protein> cross-linking induced <protein> NF-kappa B </protein> , which is known to bind to the <DNA> regulatory region </DNA> of the <DNA> long terminal repeat </DNA> ( <DNA> LTR </DNA> ) of HIV-1 and to activate HIV-1 transcription . <protein> Anti-TNF-alpha antibody </protein> but not <protein> anti-IL-1 beta antibody </protein> strongly inhibited both the induction of HIV-1 - <DNA> LTR </DNA> -driven transcription and the induction of <protein> NF-kappa B </protein> by <protein> Fc gamma R </protein> cross-linking ."
  },
  {
    "input_text": "These results indicate that Fc gamma R can mediate a TNF-alpha -dependent induction of HIV-1 gene transcription and suggest that immune complexes may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in monocytes .",
    "target_text": "These results indicate that <protein> Fc gamma R </protein> can mediate a <protein> TNF-alpha </protein> -dependent induction of <DNA> HIV-1 gene </DNA> transcription and suggest that <protein> immune complexes </protein> may contribute to the pathophysiology of HIV-1 infection by augmenting viral replication in <cell_type> monocytes </cell_type> ."
  },
  {
    "input_text": "Signalling via CD28 of human naive neonatal T lymphocytes .",
    "target_text": "Signalling via <protein> CD28 </protein> of <cell_line> human naive neonatal T lymphocytes </cell_line> ."
  },
  {
    "input_text": "Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge .",
    "target_text": "Accessory molecules play a crucial role in the development of the T cell response to antigenic challenge ."
  },
  {
    "input_text": "We have examined the role of CD28 in modulating the ' naive ' neonatal T cell response to anti-CD2 -mediated activation .",
    "target_text": "We have examined the role of <protein> CD28 </protein> in modulating the ' naive ' neonatal T cell response to <protein> anti-CD2 </protein> -mediated activation ."
  },
  {
    "input_text": "To compare the role of CD28 , neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence of anti- CD28 MoAb .",
    "target_text": "To compare the role of <protein> CD28 </protein> , <cell_type> neonatal </cell_type> and <cell_type> adult <cell_type> T cells </cell_type> </cell_type> were stimulated with a pair of <protein> mitogenic anti-CD2 antibodies </protein> in the presence or absence of <protein> anti- <protein> CD28 </protein> MoAb </protein> ."
  },
  {
    "input_text": "With anti-CD2 alone , neonatal T cells proliferated slightly but produced no detectable IL-2 , whereas adult T cells proliferated vigorously , with significant IL-2 production .",
    "target_text": "With <protein> anti-CD2 </protein> alone , <cell_type> neonatal T cells </cell_type> proliferated slightly but produced no detectable <protein> IL-2 </protein> , whereas adult <cell_type> T cells </cell_type> proliferated vigorously , with significant <protein> IL-2 </protein> production ."
  },
  {
    "input_text": "Costimulation with anti- CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells , whereas adult T cells showed only slight increases .",
    "target_text": "Costimulation with <protein> anti- <protein> CD28 </protein> MoAb </protein> greatly enhanced the proliferative response of <cell_type> neonatal <cell_type> T cells </cell_type> </cell_type> to levels equivalent to those of <cell_type> adult <cell_type> T cells </cell_type> </cell_type> , whereas <cell_type> adult <cell_type> T cells </cell_type> </cell_type> showed only slight increases ."
  },
  {
    "input_text": "Although IL-2 secretion was increased in the presence of anti- CD28 MoAb , neonatal T cell IL-2 production remained lower than in adults .",
    "target_text": "Although <protein> IL-2 </protein> secretion was increased in the presence of <protein> anti- <protein> CD28 </protein> MoAb </protein> , <cell_type> neonatal T cell </cell_type> <protein> IL-2 </protein> production remained lower than in adults ."
  },
  {
    "input_text": "In contrast , enhancement of IL-2 mRNA expression in neonates was similar to adult levels .",
    "target_text": "In contrast , enhancement of <RNA> <protein> IL-2 </protein> mRNA </RNA> expression in neonates was similar to adult levels ."
  },
  {
    "input_text": "Anti- CD28 MoAb costimulation increased NF kappa B levels in neonates , albeit to levels lower than that of adults .",
    "target_text": "Anti- <protein> <protein> CD28 </protein> MoAb </protein> costimulation increased <protein> NF kappa B </protein> levels in neonates , albeit to levels lower than that of adults ."
  },
  {
    "input_text": "The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NF kappa B induction , reduced IL-2 mRNA expression and deficient IL-2 production .",
    "target_text": "The cellular mechanism governing the diminished proliferative response of <cell_type> neonatal T lymphocytes </cell_type> to <protein> anti-CD2 </protein> may therefore be due to decreased <protein> NF kappa B </protein> induction , reduced <RNA> <protein> IL-2 </protein> mRNA </RNA> expression and deficient <protein> IL-2 </protein> production ."
  },
  {
    "input_text": "Although anti- CD28 MoAb costimulation enhances all of the above signals , NF kappa B and IL-2 levels remain lower than in adults , suggesting the need for further activation requirements in the neonate .",
    "target_text": "Although <protein> anti- <protein> CD28 </protein> MoAb </protein> costimulation enhances all of the above signals , NF kappa B and IL-2 levels remain lower than in adults , suggesting the need for further activation requirements in the neonate ."
  },
  {
    "input_text": "TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia .",
    "target_text": "TCL1 oncogene activation in <cell_type> preleukemic <cell_type> T cells </cell_type> </cell_type> from a case of ataxia-telangiectasia ."
  },
  {
    "input_text": "The TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [ t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1) ] and inversions [ inv14(q11;q32.1) ] with TCR alpha/beta loci in T-cell leukemias , such as T-prolymphocytic ( T-PLL ) .",
    "target_text": "The <DNA> TCL1 oncogene </DNA> on <DNA> human chromosome </DNA> <DNA> 14q32.1 </DNA> is involved in chromosome translocations [ <DNA> t(14;14)(q11;q32.1) </DNA> and <DNA> t(7;14)(q35;q32.1) </DNA> ] and inversions [ <DNA> inv14(q11;q32.1) </DNA> ] with <DNA> TCR alpha/beta loci </DNA> in T-cell leukemias , such as T-prolymphocytic ( T-PLL ) ."
  },
  {
    "input_text": "It is also involved in T- acute and - chronic leukemias arising in cases of ataxia-telangiectasia ( AT ) , an immunodeficiency syndrome .",
    "target_text": "It is also involved in T- acute and - chronic leukemias arising in cases of ataxia-telangiectasia ( AT ) , an immunodeficiency syndrome ."
  },
  {
    "input_text": "Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia .",
    "target_text": "Similar chromosomal rearrangements occur also in the clonally expanded <cell_type> T cells </cell_type> in AT patients before the appearance of the overt leukemia ."
  },
  {
    "input_text": "We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes ( PBLs ) from four AT cases and from healthy controls .",
    "target_text": "We have analyzed the expression of <RNA> TCL1 mRNA </RNA> and <protein> protein </protein> in <cell_type> peripheral blood lymphocytes </cell_type> ( <cell_type> PBLs </cell_type> ) from four AT cases and from healthy controls ."
  },
  {
    "input_text": "We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases .",
    "target_text": "We found that the <DNA> TCL1 gene </DNA> was overexpressed in the <cell_type> PBLs </cell_type> of an AT patient with a <cell_line> large clonal T-cell population </cell_line> exhibiting the t(14;14) translocation but not in the <cell_type> lymphocytes </cell_type> of the other cases ."
  },
  {
    "input_text": "Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14 .",
    "target_text": "Fluorescence in situ hybridization of the <DNA> TCL1 genomic locus </DNA> to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the <DNA> TCL1 locus </DNA> and is accompanied by an <DNA> inverted duplication </DNA> of the <DNA> distal part </DNA> of <DNA> chromosome 14 </DNA> ."
  },
  {
    "input_text": "These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11 .",
    "target_text": "These data indicate that <DNA> TCL1 </DNA> is activated in <cell_line> preleukemic clonal cells </cell_line> as a consequence of chromosome translocation involving sequences from the <DNA> TCR locus </DNA> at <DNA> 14q11 </DNA> ."
  },
  {
    "input_text": "Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation .",
    "target_text": "Deregulation of <DNA> TCL1 </DNA> is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation ."
  },
  {
    "input_text": "C/EBP proteins activate transcription from the human immunodeficiency virus type 1 long terminal repeat in macrophages/ monocytes .",
    "target_text": "<protein> C/EBP proteins </protein> activate transcription from the <DNA> human immunodeficiency virus type 1 long terminal repeat </DNA> in macrophages/ <cell_type> monocytes </cell_type> ."
  },
  {
    "input_text": "Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 ( HIV-1 ) long terminal repeat ( LTR ) ( V.M. Tesmer , A.Rajadhyaksha , J.Babin , and M.Bina , Proc.Natl.Acad.Sci. USA 90 : 7298-7302 , 1993 ) .",
    "target_text": "Three binding sites for <protein> C/EBP proteins </protein> are found in the <DNA> human immunodeficiency virus type 1 ( HIV-1 ) long terminal repeat </DNA> ( <DNA> LTR </DNA> ) ( V.M. Tesmer , A.Rajadhyaksha , J.Babin , and M.Bina , Proc.Natl.Acad.Sci. USA 90 : 7298-7302 , 1993 ) ."
  },
  {
    "input_text": "We have determined the functional role of C/EBP proteins and C/EBP sites in regulating transcription from the HIV- 1 LTR in monocytes /macrophages .",
    "target_text": "We have determined the functional role of <protein> C/EBP proteins </protein> and <DNA> C/EBP sites </DNA> in regulating transcription from the <DNA> HIV- 1 <DNA> LTR </DNA> </DNA> in <cell_type> <cell_type> monocytes </cell_type> /macrophages </cell_type> ."
  },
  {
    "input_text": "Inhibition of endogenous C/EBP proteins , using either an excess of C/EBP binding sites or a trans- dominant negative inhibitor , demonstrated that C/EBP proteins are required for basal and activated levels of HIV-1 LTR transcription in the promonocytic cell line U937 .",
    "target_text": "Inhibition of <protein> endogenous <protein> C/EBP proteins </protein> </protein> , using either an excess of <DNA> C/EBP binding sites </DNA> or a <DNA> trans- dominant negative inhibitor </DNA> , demonstrated that <protein> C/EBP proteins </protein> are required for basal and activated levels of <DNA> HIV-1 <DNA> LTR </DNA> </DNA> transcription in the <cell_line> promonocytic cell line U937 </cell_line> ."
  },
  {
    "input_text": "Northern ( RNA ) blots and binding assays showed that NF-IL6 is the only known C/EBP family member which is increased when U937 cells are activated .",
    "target_text": "Northern ( RNA ) blots and binding assays showed that <protein> NF-IL6 </protein> is the only known <protein> C/EBP family member </protein> which is increased when <cell_line> U937 cells </cell_line> are activated ."
  },
  {
    "input_text": "Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for normal LTR transcription both before and after cellular activation and that the two 3' C/EBP sites are functionally equivalent .",
    "target_text": "Mutational analyses of the <DNA> HIV-1 <DNA> LTR </DNA> </DNA> showed that one <DNA> C/EBP site </DNA> is required for normal <DNA> LTR </DNA> transcription both before and after cellular activation and that the two 3' <DNA> C/EBP sites </DNA> are functionally equivalent ."
  },
  {
    "input_text": "However , transcription from crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation of U937 cells .",
    "target_text": "However , transcription from <DNA> crippled HIV-1 <DNA> LTRs </DNA> </DNA> lacking <DNA> C/EBP sites </DNA> can still be induced following activation of <cell_line> U937 cells </cell_line> ."
  },
  {
    "input_text": "Several models are suggested for how elevated NF-IL6 may participate in an autostimulatory loop involving HIV infection , macrophage activation , cytokine expression , and HIV replication .",
    "target_text": "Several models are suggested for how elevated <protein> NF-IL6 </protein> may participate in an autostimulatory loop involving HIV infection , macrophage activation , <protein> cytokine </protein> expression , and HIV replication ."
  },
  {
    "input_text": "Human immunodeficiency virus type-2 gene expression : two enhancers and their activation by T-cell activators .",
    "target_text": "Human immunodeficiency virus type-2 gene expression : two <DNA> enhancers </DNA> and their activation by <cell_type> T-cell </cell_type> activators ."
  },
  {
    "input_text": "The human immunodeficiency viruses ( HIVs ) may include a spectrum of retroviruses with varying potential to infect their host , undergo long periods of latent infection , and induce pathology .",
    "target_text": "The human immunodeficiency viruses ( HIVs ) may include a spectrum of retroviruses with varying potential to infect their host , undergo long periods of latent infection , and induce pathology ."
  },
  {
    "input_text": "Since expression of the viruses is in large part regulated by the sequence elements in their long terminal repeats ( LTRs ) , this study was directed to an analysis of the regulatory elements in the HIV-2 LTR .",
    "target_text": "Since expression of the viruses is in large part regulated by the <DNA> sequence elements </DNA> in their <DNA> long terminal repeats </DNA> ( <DNA> LTRs </DNA> ) , this study was directed to an analysis of the <DNA> regulatory elements </DNA> in the <DNA> HIV-2 LTR </DNA> ."
  },
  {
    "input_text": "The HIV-2 LTR was found to contain two enhancers .",
    "target_text": "The <DNA> HIV-2 LTR </DNA> was found to contain two <DNA> enhancers </DNA> ."
  },
  {
    "input_text": "One of these enhancers is , in part , identical to the HIV-1 enhancer .",
    "target_text": "One of these <DNA> enhancers </DNA> is , in part , identical to the <DNA> HIV-1 enhancer </DNA> ."
  },
  {
    "input_text": "This enhancer in HIV-1 is the T-cell activation response element ; in HIV-2 , however , it is the second enhancer that is mainly responsible for activation in response to T-cell activators .",
    "target_text": "This <DNA> enhancer </DNA> in HIV-1 is the <DNA> T-cell activation response element </DNA> ; in HIV-2 , however , it is the <DNA> second enhancer </DNA> that is mainly responsible for activation in response to T-cell activators ."
  },
  {
    "input_text": "The second enhancer interacts with two nuclear binding proteins ( 85 kD and 27 kD mobility ) that appear to be required for optimal enhancer function and activation .",
    "target_text": "The second <DNA> enhancer </DNA> interacts with two <protein> nuclear binding proteins </protein> ( 85 kD and 27 kD mobility ) that appear to be required for optimal enhancer function and activation ."
  },
  {
    "input_text": "Observations such as these encourage the speculation that there may be subtle differences in the regulation of HIV-1 and HIV-2 expression that may be relevant to the possible longer latency and reduced pathogenicity of HIV-2 .",
    "target_text": "Observations such as these encourage the speculation that there may be subtle differences in the regulation of HIV-1 and HIV-2 expression that may be relevant to the possible longer latency and reduced pathogenicity of HIV-2 ."
  },
  {
    "input_text": "NF-M ( chicken C/EBP beta ) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line .",
    "target_text": "<protein> NF-M </protein> ( <protein> chicken C/EBP beta </protein> ) induces eosinophilic differentiation and apoptosis in a <cell_line> hematopoietic progenitor cell line </cell_line> ."
  },
  {
    "input_text": "CAAT/enhancer binding proteins ( C/EBPs ) are transcriptional activators implicated in the differentiation processes of various cell lineages .",
    "target_text": "<protein> <DNA> CAAT/enhancer </DNA> binding proteins </protein> ( <protein> C/EBPs </protein> ) are transcriptional activators implicated in the differentiation processes of various cell lineages ."
  },
  {
    "input_text": "We have shown earlier that NF-M , the chicken homolog of C/EBP beta , is specifically expressed in myelomonocytic and eosinophilic cells of the hematopoietic system .",
    "target_text": "We have shown earlier that <protein> NF-M </protein> , the <protein> chicken homolog </protein> of <protein> C/EBP beta </protein> , is specifically expressed in myelomonocytic and eosinophilic cells of the hematopoietic system ."
  },
  {
    "input_text": "To investigate the role of NF-M in hematopoietic cell lineage commitment , we constructed a conditional form of the protein by fusing it to the hormone binding domain of the human estrogen receptor .",
    "target_text": "To investigate the role of <protein> NF-M </protein> in <cell_line> hematopoietic cell lineage </cell_line> commitment , we constructed a conditional form of the protein by fusing it to the <protein> hormone binding domain </protein> of the <protein> human estrogen receptor </protein> ."
  },
  {
    "input_text": "This construct was stably expressed in a multipotent progenitor cell line transformed by the Myb-Ets oncoprotein .",
    "target_text": "This construct was stably expressed in a <cell_line> multipotent progenitor cell line </cell_line> transformed by the <protein> Myb-Ets oncoprotein </protein> ."
  },
  {
    "input_text": "We report here that both NF-M -dependent promoter constructs and resident genes could be activated by addition of beta-estradiol to the NF-M -estrogen receptor expressing progenitors .",
    "target_text": "We report here that both <DNA> <protein> NF-M </protein> -dependent promoter constructs </DNA> and resident genes could be activated by addition of beta-estradiol to the <cell_line> <protein> <protein> NF-M </protein> -estrogen receptor </protein> expressing progenitors </cell_line> ."
  },
  {
    "input_text": "At the same time , we observed a down-regulation of progenitor-specific surface markers and the up-regulation of differentiation markers restricted to the eosinophil and myeloid lineages .",
    "target_text": "At the same time , we observed a down-regulation of <protein> progenitor-specific surface markers </protein> and the up-regulation of <protein> differentiation markers </protein> restricted to the <cell_type> eosinophil </cell_type> and <cell_type> myeloid lineages </cell_type> ."
  },
  {
    "input_text": "In addition to the onset of differentiation , cell death was induced with typical apoptotic features .",
    "target_text": "In addition to the onset of differentiation , cell death was induced with typical apoptotic features ."
  },
  {
    "input_text": "Our results suggest that NF-M plays an important role in commitment along the eosinophil lineage and in the induction of apoptosis .",
    "target_text": "Our results suggest that <protein> NF-M </protein> plays an important role in commitment along the <cell_type> eosinophil lineage </cell_type> and in the induction of apoptosis ."
  },
  {
    "input_text": "Prolactin and interleukin-2 receptors in T lymphocytes signal through a MGF-STAT5-like transcription factor .",
    "target_text": "<protein> Prolactin </protein> and <protein> <protein> interleukin-2 </protein> receptors </protein> in <cell_type> T lymphocytes </cell_type> signal through a <protein> MGF-STAT5-like transcription factor </protein> ."
  },
  {
    "input_text": "The cell surface receptors for PRL and interleukin-2 ( IL-2 ) are structurally distinct , but share regulatory tasks in T lymphocytes .",
    "target_text": "The cell surface receptors for <protein> PRL </protein> and <protein> interleukin-2 </protein> ( <protein> IL-2 </protein> ) are structurally distinct , but share regulatory tasks in <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "They can stimulate proliferation and activate transcription of over-lapping sets of genes of T cells .",
    "target_text": "They can stimulate proliferation and activate transcription of over-lapping sets of genes of <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "PRL and IL-2 receptor activation are both linked to the Jak/Stat ( signal transducer and activator of transcription ) pathway .",
    "target_text": "<protein> PRL </protein> and <protein> IL-2 </protein> receptor activation are both linked to the <protein> Jak/Stat </protein> ( <protein> signal transducer and activator of transcription </protein> ) pathway ."
  },
  {
    "input_text": "We investigated the ability of PRL and IL-2 to activate Stat proteins in different T cell lines .",
    "target_text": "We investigated the ability of <protein> PRL </protein> and <protein> IL-2 </protein> to activate <protein> Stat proteins </protein> in different <cell_line> T cell lines </cell_line> ."
  },
  {
    "input_text": "The DNA binding specificities , the reactivities toward Stat-specific antisera , and the mol wt of IL-2 - and PRL -induced DNA-binding proteins in Nb2 and C196 T cell lines were investigated .",
    "target_text": "The DNA binding specificities , the reactivities toward Stat-specific antisera , and the mol wt of <protein> IL-2 </protein> - and <protein> <protein> PRL </protein> -induced DNA-binding proteins </protein> in Nb2 and C196 T cell lines were investigated ."
  },
  {
    "input_text": "A comparison with the Stat proteins induced by interferon-gamma , PRL , and IL-6 in T47D mammary tumor cells was made .",
    "target_text": "A comparison with the <protein> Stat proteins </protein> induced by <protein> interferon-gamma </protein> , <protein> PRL </protein> , and <protein> IL-6 </protein> in <cell_line> T47D mammary tumor cells </cell_line> was made ."
  },
  {
    "input_text": "We found that these parameters were indistinguishable for one of the PRL- and IL-2- induced factors .",
    "target_text": "We found that these parameters were indistinguishable for one of the PRL- and IL-2- induced factors ."
  },
  {
    "input_text": "A transcription factor closely related to mammary gland factor-Stat5 is rapidly activated upon interaction of IL-2 and PRL with their respective receptors .",
    "target_text": "A transcription factor closely related to <protein> mammary gland factor-Stat5 </protein> is rapidly activated upon interaction of <protein> IL-2 </protein> and <protein> PRL </protein> with their respective receptors ."
  },
  {
    "input_text": "Activation of a second protein related to Stat1 was also observed .",
    "target_text": "Activation of a second protein related to <protein> Stat1 </protein> was also observed ."
  },
  {
    "input_text": "Our results emphasize the role of PRL as a regulator of the immune response and indicate that the Stat factors mammary gland factor-Stat5 and Stat1 play a role in the regulation of gene expression during T cell development .",
    "target_text": "Our results emphasize the role of <protein> PRL </protein> as a regulator of the immune response and indicate that the <protein> Stat factors </protein> <protein> mammary gland factor-Stat5 </protein> and <protein> Stat1 </protein> play a role in the regulation of gene expression during T cell development ."
  },
  {
    "input_text": "ETS1 transactivates the human GM-CSF promoter in Jurkat T cells stimulated with PMA and ionomycin .",
    "target_text": "<protein> ETS1 </protein> transactivates the <DNA> human GM-CSF promoter </DNA> in <cell_line> Jurkat T cells </cell_line> stimulated with PMA and ionomycin ."
  },
  {
    "input_text": "Activation of T helper cells results in coordinate expression of a number of cytokines involved in differentiation , proliferation and activation of the haematopoietic system .",
    "target_text": "Activation of <cell_type> T helper cells </cell_type> results in coordinate expression of a number of <protein> cytokines </protein> involved in differentiation , proliferation and activation of the haematopoietic system ."
  },
  {
    "input_text": "Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) is one such cytokine whose increased expression results partly from increases in transcription .",
    "target_text": "<protein> Granulocyte-macrophage colony-stimulating factor </protein> ( <protein> GM-CSF </protein> ) is one such <protein> cytokine </protein> whose increased expression results partly from increases in transcription ."
  },
  {
    "input_text": "Cis-acting elements with NF kappa B , AP-1 and ETS-like motifs have been identified in the promoter region of the GM-CSF gene , which are important for transcriptional activity following PMA and ionomycin stimulation .",
    "target_text": "<DNA> Cis-acting elements </DNA> with <DNA> <protein> NF kappa B </protein> </DNA> , <DNA> <protein> AP-1 </protein> </DNA> and <DNA> ETS-like motifs </DNA> have been identified in the promoter region of the <DNA> <protein> GM-CSF </protein> gene </DNA> , which are important for transcriptional activity following PMA and ionomycin stimulation ."
  },
  {
    "input_text": "A number of the ETS family of transcription factors are expressed in T cells , including ETS1 and ELF1 .",
    "target_text": "A number of the <protein> ETS family </protein> of <protein> transcription factors </protein> are expressed in <cell_type> T cells </cell_type> , including <protein> ETS1 </protein> and <protein> ELF1 </protein> ."
  },
  {
    "input_text": "Here we describe the ability of these factors to interact with a site ( GM5 ) , located within the CLE0 element , -47 to -40 upstream of the GM-CSF transcription initiation site .",
    "target_text": "Here we describe the ability of these factors to interact with a site ( <DNA> GM5 </DNA> ) , located within the <DNA> CLE0 element </DNA> , <DNA> -47 to -40 upstream </DNA> of the <DNA> <protein> GM-CSF </protein> transcription initiation site </DNA> ."
  },
  {
    "input_text": "Exogenous ETS1 , but not ELF1 , can transactivate GM-CSF , through the GM5 site , in a PMA / ionomycin dependent manner .",
    "target_text": "Exogenous <protein> ETS1 </protein> , but not <protein> ELF1 </protein> , can transactivate <protein> GM-CSF </protein> , through the <DNA> GM5 </DNA> site , in a PMA / ionomycin dependent manner ."
  },
  {
    "input_text": "Other unidentified ETS-like factors present in Jurkat cells are also capable of binding GM5 .",
    "target_text": "Other unidentified <protein> ETS-like factors </protein> present in <cell_line> Jurkat cells </cell_line> are also capable of binding <DNA> GM5 </DNA> ."
  },
  {
    "input_text": "Mutation of the core ETS binding site from -GGAA- to -GGAT- prevents the binding of ETS-like factors with the exception of ETS1 .",
    "target_text": "Mutation of the core <DNA> ETS binding site </DNA> from <DNA> -GGAA- to -GGAT- </DNA> prevents the binding of <protein> ETS-like factors </protein> with the exception of <protein> ETS1 </protein> ."
  },
  {
    "input_text": "The GM-CSF promoter , modified in this way to be ETS1 specific , is fully responsive to PMA / ionomycin induction , in addition to ETS1 transactivation in the presence of PMA and ionomycin .",
    "target_text": "The <DNA> <protein> GM-CSF </protein> promoter </DNA> , modified in this way to be <protein> ETS1 </protein> specific , is fully responsive to PMA / ionomycin induction , in addition to <protein> ETS1 </protein> transactivation in the presence of PMA and ionomycin ."
  },
  {
    "input_text": "Together these data suggest that ETS1 may be involved in mediating the increased GM-CSF production associated with T cell activation .",
    "target_text": "Together these data suggest that <protein> ETS1 </protein> may be involved in mediating the increased <protein> GM-CSF </protein> production associated with <cell_type> T cell </cell_type> activation ."
  },
  {
    "input_text": "Quantitation of beta 1 triiodothyronine receptor mRNA in human tissues by competitive reverse transcription polymerase chain reaction .",
    "target_text": "Quantitation of <RNA> <protein> beta 1 triiodothyronine receptor </protein> mRNA </RNA> in human tissues by competitive reverse transcription polymerase chain reaction ."
  },
  {
    "input_text": "Thyroid hormones act by binding to nuclear receptor proteins , the thyroid hormone receptors ( TR ) alpha and beta .",
    "target_text": "Thyroid hormones act by binding to <protein> nuclear receptor proteins </protein> , the <protein> thyroid hormone receptors </protein> ( <protein> TR </protein> ) alpha and beta ."
  },
  {
    "input_text": "Data from cell culture and animal studies indicate that TR expression may be regulated to modulate target organ responsiveness to thyroid hormone .",
    "target_text": "Data from cell culture and animal studies indicate that <protein> TR </protein> expression may be regulated to modulate target organ responsiveness to thyroid hormone ."
  },
  {
    "input_text": "To investigate whether such adaptive changes in TR expression occur in humans , we determined the mRNA levels of the hTR beta 1 in various thyroid states .",
    "target_text": "To investigate whether such adaptive changes in <protein> TR </protein> expression occur in humans , we determined the mRNA levels of the <protein> hTR beta 1 </protein> in various thyroid states ."
  },
  {
    "input_text": "Patients with overt hypo - or hyper thyroidism were enrolled in the study .",
    "target_text": "Patients with overt hypo - or hyper thyroidism were enrolled in the study ."
  },
  {
    "input_text": "Total RNA was isolated from peripheral blood mononuclear cells and hTR beta 1 mRNA levels determined by quantitative competitive reverse transcription PCR .",
    "target_text": "<RNA> Total RNA </RNA> was isolated from <cell_type> peripheral blood mononuclear cells </cell_type> and <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels determined by quantitative competitive reverse transcription PCR ."
  },
  {
    "input_text": "For comparison , hTR beta 1 mRNA levels were determined in lymphocytes and normal thyroid tissue of euthyroid patients .",
    "target_text": "For comparison , <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels were determined in <cell_type> lymphocytes </cell_type> and normal thyroid tissue of euthyroid patients ."
  },
  {
    "input_text": "Human TR beta 1 mRNA levels in lymphocytes were 1.8 +/- 0.4 , 1.9 +/- 0.5 , 1.1 +/- 0.4 10 ( -18 ) mol/microgram RNA in hypo - , eu - and hyper thyroid patients , respectively , corresponding to an estimated 0.5 -2 molecules per cell .",
    "target_text": "<RNA> <protein> Human TR beta 1 </protein> mRNA </RNA> levels in <cell_type> lymphocytes </cell_type> were 1.8 +/- 0.4 , 1.9 +/- 0.5 , 1.1 +/- 0.4 10 ( -18 ) mol/microgram RNA in hypo - , eu - and hyper thyroid patients , respectively , corresponding to an estimated 0.5 -2 molecules per cell ."
  },
  {
    "input_text": "Although the mean hTR beta 1 mRNA levels were 40 % lower in hyperthyroid than in euthyroid subjects , this difference did not reach statistical significance .",
    "target_text": "Although the mean <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels were 40 % lower in hyperthyroid than in euthyroid subjects , this difference did not reach statistical significance ."
  },
  {
    "input_text": "Similar levels of hTR beta 1 mRNA levels were detected in thyroid gland from euthyroid patients .",
    "target_text": "Similar levels of <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels were detected in thyroid gland from euthyroid patients ."
  },
  {
    "input_text": "In summary , we developed an assay for the quantitative determination of hTR beta 1 mRNA levels in small human tissue samples , containing as little as 50 ng of total RNA .",
    "target_text": "In summary , we developed an assay for the quantitative determination of <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels in small human tissue samples , containing as little as 50 ng of total RNA ."
  },
  {
    "input_text": "Absolute hTR beta 1 mRNA levels are very low with an estimated one molecule of mRNA being present in a mononuclear blood cell or thyrocyte .",
    "target_text": "Absolute <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels are very low with an estimated one molecule of <RNA> mRNA </RNA> being present in a <cell_type> mononuclear blood cell </cell_type> or <cell_type> thyrocyte </cell_type> ."
  },
  {
    "input_text": "No up-regulation of hTR beta 1 was seen in hypothyroid relative to euthyroid patients .",
    "target_text": "No up-regulation of <protein> hTR beta 1 </protein> was seen in hypothyroid relative to euthyroid patients ."
  },
  {
    "input_text": "However , there is a non-significant trend towards a down-regulation of hTR beta 1 mRNA levels in hyperthyroid patients .",
    "target_text": "However , there is a non-significant trend towards a down-regulation of <RNA> <protein> hTR beta 1 </protein> mRNA </RNA> levels in hyperthyroid patients ."
  },
  {
    "input_text": "Multiple proteins interact with the nuclear inhibitory protein repressor element in the human interleukin-3 promoter .",
    "target_text": "Multiple <protein> proteins </protein> interact with the <DNA> nuclear inhibitory protein repressor element </DNA> in the <DNA> human interleukin-3 promoter </DNA> ."
  },
  {
    "input_text": "T cell expression of interleukin 3 ( IL-3 ) is directed by positive and negative cis-acting DNA elements clustered within 300 base pairs of the transcriptional start site .",
    "target_text": "T cell expression of <protein> interleukin 3 </protein> ( <protein> IL-3 </protein> ) is directed by positive and negative cis-acting DNA elements clustered within 300 base pairs of the <DNA> transcriptional start site </DNA> ."
  },
  {
    "input_text": "A strong repressor element , termed nuclear inhibitory protein ( NIP ) , was previously mapped to a segment of the IL-3 promoter between nucleotides -271 and -250 .",
    "target_text": "A strong <protein> repressor element </protein> , termed <protein> nuclear inhibitory protein </protein> ( <protein> NIP </protein> ) , was previously mapped to a segment of the <DNA> IL-3 promoter </DNA> between <DNA> nucleotides -271 and -250 </DNA> ."
  },
  {
    "input_text": "Functional characterization of this element demonstrates that it can mediate repression when linked in cis to a heterologous promoter .",
    "target_text": "Functional characterization of this element demonstrates that it can mediate repression when linked in cis to a <DNA> heterologous promoter </DNA> ."
  },
  {
    "input_text": "DNA binding experiments were carried out to characterize the repressor activity .",
    "target_text": "DNA binding experiments were carried out to characterize the repressor activity ."
  },
  {
    "input_text": "Using varying conditions , three distinct complexes were shown to interact specifically with the NIP region , although only one correlates with repressor activity .",
    "target_text": "Using varying conditions , three distinct complexes were shown to interact specifically with the <DNA> <protein> NIP </protein> region </DNA> , although only one correlates with repressor activity ."
  },
  {
    "input_text": "Complex 1 results from binding of a ubiquitous polypeptide that recognizes the 3' portion of this sequence and is not required for repression .",
    "target_text": "<protein> Complex 1 </protein> results from binding of a ubiquitous polypeptide that recognizes the <DNA> 3' portion </DNA> of this sequence and is not required for repression ."
  },
  {
    "input_text": "Complex 2 corresponds to binding of transcription factor ( upstream stimulatory factor ) to an E-box motif in the 5' portion of the NIP region .",
    "target_text": "<protein> Complex 2 </protein> corresponds to binding of <protein> transcription factor </protein> ( <protein> upstream stimulatory factor </protein> ) to an <DNA> E-box motif </DNA> in the <DNA> 5' portion </DNA> of the <DNA> <protein> NIP </protein> region </DNA> ."
  },
  {
    "input_text": "DNA binding specificity of complex 3 overlaps with that of upstream stimulatory factor but is clearly distinct .",
    "target_text": "DNA binding specificity of complex 3 overlaps with that of <protein> upstream stimulatory factor </protein> but is clearly distinct ."
  },
  {
    "input_text": "To determine which of the latter two complexes represents NIP activity , we incorporated small alterations into the NIP site of an IL-3 promoter -linked reporter construct and examined their effects on NIP -mediated repression .",
    "target_text": "To determine which of the latter two complexes represents <protein> NIP </protein> activity , we incorporated small alterations into the <DNA> <protein> NIP </protein> site </DNA> of an <DNA> <DNA> IL-3 promoter </DNA> -linked reporter construct </DNA> and examined their effects on <protein> NIP </protein> -mediated repression ."
  },
  {
    "input_text": "Functional specificity for repression matches the DNA binding specificity of complex 3 ; both repressor activity and complex 3 binding require the consensus sequence CTCACNTNC .",
    "target_text": "Functional specificity for repression matches the DNA binding specificity of <protein> complex 3 </protein> ; both repressor activity and <protein> complex 3 </protein> binding require the <DNA> consensus sequence </DNA> CTCACNTNC ."
  },
  {
    "input_text": "The hematopoietic transcription factor PU.1 is downregulated in human multiple myeloma cell lines .",
    "target_text": "The <protein> hematopoietic transcription factor </protein> <protein> PU.1 </protein> is downregulated in <cell_line> human multiple myeloma cell lines </cell_line> ."
  },
  {
    "input_text": "PU.1 is a hematopoietic transcription factor belonging to the Ets-family .",
    "target_text": "<protein> PU.1 </protein> is a <protein> hematopoietic transcription factor </protein> belonging to the <protein> Ets-family </protein> ."
  },
  {
    "input_text": "It is identical to the Spi-1 oncogene , which is implicated in spleen focus-forming virus-induced murine erythroleukemias .",
    "target_text": "It is identical to the <DNA> Spi-1 oncogene </DNA> , which is implicated in spleen focus-forming virus-induced murine erythroleukemias ."
  },
  {
    "input_text": "PU.1 seems to be required for early development of multiple hematopoietic lineages , but its expression in mature cells is preferentially observed in cells of the B-cell-and monocyte/macrophage- differentiation lineage .",
    "target_text": "<protein> PU.1 </protein> seems to be required for early development of <cell_type> multiple hematopoietic lineages </cell_type> , but its expression in <cell_type> mature cells </cell_type> is preferentially observed in cells of the <cell_type> B-cell-and monocyte/macrophage- differentiation lineage </cell_type> ."
  },
  {
    "input_text": "It binds the so-called Pu box , an important tissue-specific regulatory DNA element present in a number of genes expressed in these cell lineages .",
    "target_text": "It binds the so-called <DNA> Pu box </DNA> , an important <DNA> tissue-specific regulatory DNA element </DNA> present in a number of genes expressed in these <cell_type> cell lineages </cell_type> ."
  },
  {
    "input_text": "We have analyzed the expression and activity of PU.1 during human B-cell development using a panel of B-cell lines representing different stages of maturation , from early precursors to differentiated plasma cells .",
    "target_text": "We have analyzed the expression and activity of <protein> PU.1 </protein> during human B-cell development using a panel of <cell_line> B-cell lines </cell_line> representing different stages of maturation , from <cell_line> early precursors </cell_line> to <cell_line> differentiated plasma cells </cell_line> ."
  },
  {
    "input_text": "PU.1 mRNA expression and PU.1 DNA binding activity , as measured by Northern blot analysis and electrophoretic mobility shift assay , respectively , were evident in cell lines representing pro-B , pre-B , and mature B cells .",
    "target_text": "<RNA> <protein> PU.1 </protein> mRNA </RNA> expression and <protein> PU.1 </protein> DNA binding activity , as measured by Northern blot analysis and electrophoretic mobility shift assay , respectively , were evident in <cell_line> cell lines </cell_line> representing pro-B , pre-B , and mature B cells ."
  },
  {
    "input_text": "We could also show Pu box -dependent transactivation of a reporter gene in transient transfections in these cell lines .",
    "target_text": "We could also show <DNA> Pu box </DNA> -dependent transactivation of a reporter gene in transient transfections in these <cell_line> cell lines </cell_line> ."
  },
  {
    "input_text": "In contrast , in a number of multiple myeloma cell lines , representing differentiated , plasma cell-like B cells , PU.1 DNA binding activity , mRNA expression , and Pu box -dependent transactivation were absent or detectable at a very low level .",
    "target_text": "In contrast , in a number of <cell_line> multiple myeloma cell lines </cell_line> , representing <cell_type> differentiated , plasma cell-like B cells </cell_type> , <protein> PU.1 </protein> DNA binding activity , mRNA expression , and <DNA> Pu box </DNA> -dependent transactivation were absent or detectable at a very low level ."
  },
  {
    "input_text": "In lymphoblastoid cell lines , which exemplify an intermediate stage of B-cell differentiation , a reduced expression and activity were observed .",
    "target_text": "In <cell_line> lymphoblastoid cell lines </cell_line> , which exemplify an intermediate stage of B-cell differentiation , a reduced expression and activity were observed ."
  },
  {
    "input_text": "The findings in the human multiple myeloma cell lines represent the first examples of B cells with downregulated PU.1 expression and apparently contradict observations in the murine system in which PU.1 is expressed and active in plasmacytoma cell lines .",
    "target_text": "The findings in the <cell_line> human <cell_line> multiple myeloma cell lines </cell_line> </cell_line> represent the first examples of <cell_type> B cells </cell_type> with downregulated <protein> PU.1 </protein> expression and apparently contradict observations in the murine system in which <protein> PU.1 </protein> is expressed and active in <cell_line> plasmacytoma cell lines </cell_line> ."
  },
  {
    "input_text": "At present , it is unclear whether the lack of PU.1 expression and activity in human multiple myeloma cell lines represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in terminally differentiated B cells .",
    "target_text": "At present , it is unclear whether the lack of <protein> PU.1 </protein> expression and activity in <cell_line> human <cell_line> multiple myeloma cell lines </cell_line> </cell_line> represents a malignancy-associated defect in these cells or exemplifies a normal developmental regulation in <cell_type> terminally differentiated <cell_type> B cells </cell_type> </cell_type> ."
  },
  {
    "input_text": "Regulation of granulocyte-macrophage colony-stimulating factor and E-selectin expression in endothelial cells by cyclosporin A and the T-cell transcription factor NFAT .",
    "target_text": "Regulation of <protein> granulocyte-macrophage colony-stimulating factor </protein> and <protein> E-selectin </protein> expression in <cell_type> endothelial cells </cell_type> by cyclosporin A and the <protein> T-cell transcription factor </protein> <protein> NFAT </protein> ."
  },
  {
    "input_text": "Nuclear factor of activated T cells ( NFAT ) was originally described as a T-cell-specific transcription factor athat supported the activation of cytokine gene expression and mediated the immunoregulatory effects of cyclosporin A ( CsA ) .",
    "target_text": "<protein> Nuclear factor of activated T cells </protein> ( <protein> NFAT </protein> ) was originally described as a <protein> T-cell-specific transcription factor </protein> athat supported the activation of <protein> cytokine </protein> gene expression and mediated the <protein> immunoregulatory </protein> effects of cyclosporin A ( CsA ) ."
  },
  {
    "input_text": "As we observed that activated endothelial cells also expressed NFAT , we tested the antiinflammatory properties of CsA in endothelial cells .",
    "target_text": "As we observed that <cell_type> activated endothelial cells </cell_type> also expressed <protein> NFAT </protein> , we tested the antiinflammatory properties of CsA in <cell_type> endothelial cells </cell_type> ."
  },
  {
    "input_text": "Significantly , CsA completely suppressed the induction of NFAT in endothelial cells and inhibited the activity of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) gene regulatory elements that use NFAT by 60 % .",
    "target_text": "Significantly , CsA completely suppressed the induction of <protein> NFAT </protein> in <cell_type> endothelial cells </cell_type> and inhibited the activity of <DNA> <protein> granulocyte-macrophage colony-stimulating factor </protein> ( <protein> GM-CSF </protein> ) gene regulatory elements </DNA> that use <protein> NFAT </protein> by 60 % ."
  },
  {
    "input_text": "CsA similarly mediated a reduction of up to 65 % in GM-CSF mRNA and protein expression in activated endothelial cells .",
    "target_text": "CsA similarly mediated a reduction of up to 65 % in <RNA> <protein> GM-CSF </protein> mRNA </RNA> and protein expression in <cell_type> activated endothelial cells </cell_type> ."
  },
  {
    "input_text": "CsA also suppressed E-selectin , but not vascular cell adhesion molecule-1 ( VCAM-1 ) expression in endothelial cells , even though the E-selectin promoter is activated by NF-kappa B rather than NFAT .",
    "target_text": "CsA also suppressed <protein> E-selectin </protein> , but not <protein> vascular cell adhesion molecule-1 </protein> ( <protein> VCAM-1 </protein> ) expression in endothelial cells , even though the <DNA> <protein> E-selectin </protein> promoter </DNA> is activated by <protein> NF-kappa B </protein> rather than <protein> NFAT </protein> ."
  },
  {
    "input_text": "Hence , induction of cell surface expression of this leukocyte adhesion molecule by tumor necrosis factor ( TNF ) -alpha was reduced by 40 % in the presence of CsA , and this was reflected by a 29 % decrease in neutrophil adhesion .",
    "target_text": "Hence , induction of cell surface expression of this <protein> leukocyte adhesion molecule </protein> by <protein> tumor necrosis factor ( TNF ) -alpha </protein> was reduced by 40 % in the presence of CsA , and this was reflected by a 29 % decrease in <cell_type> neutrophil </cell_type> adhesion ."
  },
  {
    "input_text": "The effects of CsA on endothelial cells were also detected at the chromatin structure level , as DNasel hypersensitive sites within both the GM-CSF enhancer and the E-selectin promoter were suppressed by CsA .",
    "target_text": "The effects of CsA on <cell_type> endothelial cells </cell_type> were also detected at the <DNA> chromatin </DNA> structure level , as <DNA> <protein> DNasel </protein> hypersensitive sites </DNA> within both the <protein> GM-CSF </protein> enhancer and the <DNA> <protein> E-selectin </protein> promoter </DNA> were suppressed by CsA ."
  },
  {
    "input_text": "This represents the first report of NFAT in endothelial cells and suggests mechanisms by which CsA could function as an antiinflammatory agent .",
    "target_text": "This represents the first report of <protein> NFAT </protein> in <cell_type> endothelial cells </cell_type> and suggests mechanisms by which CsA could function as an antiinflammatory agent ."
  },
  {
    "input_text": "Costimulation requirement for AP-1 and NF-kappa B transcription factor activation in T cells .",
    "target_text": "Costimulation requirement for <protein> AP-1 </protein> and <protein> NF-kappa B </protein> transcription factor activation in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "The transcriptional activity of the IL-2 promoter requires T-cell costimulation delivered by the TCR and the auxiliary receptor CD28 .",
    "target_text": "The transcriptional activity of the <DNA> <protein> IL-2 </protein> promoter </DNA> requires <cell_type> T-cell </cell_type> costimulation delivered by the <protein> TCR </protein> and the <protein> auxiliary receptor CD28 </protein> ."
  },
  {
    "input_text": "Several transcription factors participate in IL-2 promoter activation , among which are AP-1 -like factors and NF-kappa B .",
    "target_text": "Several <protein> transcription factors </protein> participate in <protein> IL-2 </protein> promoter activation , among which are <protein> <protein> AP-1 </protein> -like factors </protein> and <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "Protein phosphorylation has an important role in the regulation of these two factors : ( 1 ) it induces the transactivating capacity of the AP-1 protein c-Jun ; and ( 2 ) it is involved in the release of the cytoplasmic inhibitor , I kappa B , from NF-kappa B , allowing translocation of the latter into the nucleus .",
    "target_text": "Protein phosphorylation has an important role in the regulation of these two factors : ( 1 ) it induces the transactivating capacity of the <protein> AP-1 protein </protein> <protein> c-Jun </protein> ; and ( 2 ) it is involved in the release of the <protein> cytoplasmic inhibitor </protein> , <protein> I kappa B </protein> , from <protein> NF-kappa B </protein> , allowing translocation of the latter into the nucleus ."
  },
  {
    "input_text": "We have recently shown that both phosphorylation processes require T-cell costimulation .",
    "target_text": "We have recently shown that both phosphorylation processes require T-cell costimulation ."
  },
  {
    "input_text": "Furthermore , in activated T cells , the kinetics of the two phosphorylation events are essentially similar .",
    "target_text": "Furthermore , in <cell_type> activated T cells </cell_type> , the kinetics of the two phosphorylation events are essentially similar ."
  },
  {
    "input_text": "According to our results , however , the kinases responsible for the two processes are distinct entities .",
    "target_text": "According to our results , however , the kinases responsible for the two processes are distinct entities ."
  },
  {
    "input_text": "Whereas TPCK inhibits phosphorylation of I kappa B and , consequently , activation of NF-kappa B , it markedly enhances the activity of JNK , the MAP kinase-related kinase that phosphorylates the transactivation domain of c-Jun .",
    "target_text": "Whereas <protein> TPCK </protein> inhibits phosphorylation of <protein> I kappa B </protein> and , consequently , activation of <protein> NF-kappa B </protein> , it markedly enhances the activity of <protein> JNK </protein> , the <protein> MAP kinase-related kinase </protein> that phosphorylates the <protein> transactivation domain </protein> of <protein> c-Jun </protein> ."
  },
  {
    "input_text": "We , therefore , propose the activation scheme presented in FIGURE 3 for T-cell costimulation .",
    "target_text": "We , therefore , propose the activation scheme presented in FIGURE 3 for T-cell costimulation ."
  },
  {
    "input_text": "Costimulation results in the activation of a signaling pathway that leads to the simultaneous induction of the two transcription factors , AP-1 and NF-kappa B .",
    "target_text": "Costimulation results in the activation of a signaling pathway that leads to the simultaneous induction of the two <protein> transcription factors </protein> , <protein> AP-1 </protein> and <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "Integration of the signals generated by TCR and CD28 engagement occurs along this pathway , which then bifurcates to induce I kappa B phosphorylation and NF-kappa B activation on the one hand , and JNK activation and c-Jun phosphorylation on the other .",
    "target_text": "Integration of the signals generated by <protein> TCR </protein> and <protein> CD28 </protein> engagement occurs along this pathway , which then bifurcates to induce <protein> I kappa B </protein> phosphorylation and <protein> NF-kappa B </protein> activation on the one hand , and <protein> JNK </protein> activation and <protein> c-Jun </protein> phosphorylation on the other ."
  },
  {
    "input_text": "We are currently engaged in defining where the two signals integrate along the AP-1 / NF-kappa B pathway .",
    "target_text": "We are currently engaged in defining where the two signals integrate along the <protein> AP-1 </protein> / <protein> NF-kappa B </protein> pathway ."
  },
  {
    "input_text": "Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B /Rel transcription factors .",
    "target_text": "Regulation of human immunodeficiency virus type 1 and cytokine gene expression in <cell_type> myeloid cells </cell_type> by <protein> <protein> NF-kappa B </protein> /Rel </protein> <protein> transcription factors </protein> ."
  },
  {
    "input_text": "CD4+ macrophages in tissues such as lung , skin , and lymph nodes , promyelocytic cells in bone marrow , and peripheral blood monocytes serve as important targets and reservoirs for human immunodeficiency virus type 1 ( HIV-1 ) replication .",
    "target_text": "<cell_line> CD4+ macrophages </cell_line> in tissues such as lung , skin , and lymph nodes , <cell_type> promyelocytic cells </cell_type> in bone marrow , and <cell_type> peripheral blood monocytes </cell_type> serve as important targets and reservoirs for human immunodeficiency virus type 1 ( HIV-1 ) replication ."
  },
  {
    "input_text": "HIV-1 -infected myeloid cells are often diminished in their ability to participate in chemotaxis , phagocytosis , and intracellular killing .",
    "target_text": "HIV-1 -infected <cell_type> myeloid cells </cell_type> are often diminished in their ability to participate in chemotaxis , phagocytosis , and intracellular killing ."
  },
  {
    "input_text": "HIV-1 infection of myeloid cells can lead to the expression of surface receptors associated with cellular activation and/or differentiation that increase the responsiveness of these cells to cytokines secreted by neighboring cells as well as to bacteria or other pathogens .",
    "target_text": "HIV-1 infection of <cell_type> myeloid cells </cell_type> can lead to the expression of <protein> surface receptors </protein> associated with cellular activation and/or differentiation that increase the responsiveness of these cells to <protein> cytokines </protein> secreted by neighboring cells as well as to bacteria or other pathogens ."
  },
  {
    "input_text": "Enhancement of HIV-1 replication is related in part to increased DNA-binding activity of cellular transcription factors such as NF-kappa B .",
    "target_text": "Enhancement of HIV-1 replication is related in part to increased DNA-binding activity of <protein> cellular <protein> transcription factors </protein> </protein> such as <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "NF-kappa B binds to the HIV-1 enhancer region of the long terminal repeat and contributes to the inducibility of HIV-1 gene expression in response to multiple activating agents .",
    "target_text": "<protein> NF-kappa B </protein> binds to the <DNA> HIV-1 enhancer </DNA> region of the <DNA> long terminal repeat </DNA> and contributes to the inducibility of HIV-1 gene expression in response to multiple activating agents ."
  },
  {
    "input_text": "Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding activity .",
    "target_text": "Phosphorylation and degradation of the <protein> cytoplasmic inhibitor </protein> <protein> I kappa B </protein> alpha are crucial regulatory events in the activation of <protein> NF-kappa B </protein> DNA-binding activity ."
  },
  {
    "input_text": "Both N- and C- terminal residues of I kappa B alpha are required for inducer-mediated degradation .",
    "target_text": "Both N- and C- terminal residues of <protein> I kappa B </protein> alpha are required for inducer-mediated degradation ."
  },
  {
    "input_text": "Chronic HIV-1 infection of myeloid cells leads to constitutive NF-kappa B DNA-binding activity and provides an intranuclear environment capable of perpetuating HIV-1 replication .",
    "target_text": "Chronic HIV-1 infection of <cell_type> myeloid cells </cell_type> leads to constitutive <protein> NF-kappa B </protein> DNA-binding activity and provides an intranuclear environment capable of perpetuating HIV-1 replication ."
  },
  {
    "input_text": "Increased intracellular stores of latent NF-kappa B may also result in rapid inducibility of NF-kappa B -dependent cytokine gene expression .",
    "target_text": "Increased intracellular stores of <protein> latent <protein> NF-kappa B </protein> </protein> may also result in rapid inducibility of <protein> NF-kappa B </protein> -dependent <protein> cytokine </protein> gene expression ."
  },
  {
    "input_text": "In response to secondary pathogenic infections or antigenic challenge , cytokine gene expression is rapidly induced , enhanced , and sustained over prolonged periods in HIV-1 -infected myeloid cells compared with uninfected cells .",
    "target_text": "In response to secondary pathogenic infections or antigenic challenge , <protein> cytokine </protein> gene expression is rapidly induced , enhanced , and sustained over prolonged periods in <cell_line> HIV-1 -infected <cell_type> myeloid cells </cell_type> </cell_line> compared with <cell_type> uninfected cells </cell_type> ."
  },
  {
    "input_text": "Elevated levels of several inflammatory cytokines have been detected in the sera of HIV-1 -infected individuals .",
    "target_text": "Elevated levels of several <protein> inflammatory cytokines </protein> have been detected in the sera of HIV-1 -infected individuals ."
  },
  {
    "input_text": "Secretion of myeloid cell-derived cytokines may both increase virus production and contribute to AIDS-associated disorders .",
    "target_text": "Secretion of <protein> myeloid cell-derived <protein> cytokines </protein> </protein> may both increase virus production and contribute to AIDS-associated disorders ."
  },
  {
    "input_text": "Steroid mediated lysis of lymphoblasts requires the DNA binding region of the steroid hormone receptor .",
    "target_text": "Steroid mediated lysis of <cell_type> lymphoblasts </cell_type> requires the DNA binding region of the steroid hormone receptor ."
  },
  {
    "input_text": "Glucocorticoids kill certain types of lymphoblasts , but the mechanisms are unknown .",
    "target_text": "Glucocorticoids kill certain types of <cell_type> lymphoblasts </cell_type> , but the mechanisms are unknown ."
  },
  {
    "input_text": "It is clear that sufficient numbers of functional glucocorticoid receptors are required to mediate lysis , but whether they do so through the classical model of steroid hormone activation and modulation of gene expression has not been established .",
    "target_text": "It is clear that sufficient numbers of functional <protein> glucocorticoid receptors </protein> are required to mediate lysis , but whether they do so through the classical model of steroid hormone activation and modulation of gene expression has not been established ."
  },
  {
    "input_text": "In this report we have asked which region ( s ) of the steroid receptor are important for mediating lysis in leukemic T lymphoblasts .",
    "target_text": "In this report we have asked which region ( s ) of the <protein> steroid receptor </protein> are important for mediating lysis in <cell_type> leukemic T <cell_type> lymphoblasts </cell_type> </cell_type> ."
  },
  {
    "input_text": "CEM-ICR 27 leukemic lymphoblasts , a clone of CEM cells which lack functional glucocorticoid receptors and therefore are neither lysed by dexamethasone nor capable of showing glutamine synthetase induction , were provided with steroid receptors by DNA transfections of various receptor gene constructs .",
    "target_text": "<cell_line> CEM-ICR 27 leukemic <cell_type> lymphoblasts </cell_type> </cell_line> , a clone of <cell_line> CEM cells </cell_line> which lack functional <protein> glucocorticoid receptors </protein> and therefore are neither lysed by dexamethasone nor capable of showing <protein> glutamine synthetase </protein> induction , were provided with <protein> steroid receptors </protein> by DNA transfections of various receptor gene constructs ."
  },
  {
    "input_text": "We measured steroid mediated lysis , receptor number and induction of glutamine synthetase in the transfected cells .",
    "target_text": "We measured steroid mediated lysis , receptor number and induction of <protein> glutamine synthetase </protein> in the <cell_line> transfected cells </cell_line> ."
  },
  {
    "input_text": "Our results provide evidence that the lysis mechanism in the ICR27 lymphoblasts is restored when functional receptor number is restored .",
    "target_text": "Our results provide evidence that the lysis mechanism in the <cell_line> ICR27 <cell_type> lymphoblasts </cell_type> </cell_line> is restored when functional receptor number is restored ."
  },
  {
    "input_text": "The DNA binding region specifying high affinity for GRE sites is required .",
    "target_text": "The <protein> DNA binding region </protein> specifying high affinity for <DNA> GRE sites </DNA> is required ."
  },
  {
    "input_text": "Lysis is mediated by any steroid that allows for activation of the receptor containing such a region .",
    "target_text": "Lysis is mediated by any steroid that allows for activation of the receptor containing such a region ."
  },
  {
    "input_text": "Our data support the view that steroid -mediated cell death occurs by a process requiring direct interaction of steroid -receptor complexes with the genome .",
    "target_text": "Our data support the view that steroid -mediated cell death occurs by a process requiring direct interaction of <protein> steroid -receptor complexes </protein> with the genome ."
  },
  {
    "input_text": "Functional characterization of the murine homolog of the B cell-specific coactivator BOB.1/OBF.1 .",
    "target_text": "Functional characterization of the <protein> murine homolog </protein> of the <protein> B cell-specific coactivator </protein> <protein> BOB.1/OBF.1 </protein> ."
  },
  {
    "input_text": "B cell-specific transcriptional promoter activity mediated by the octamer motif requires the Oct1 or Oct2 protein and additional B cell-restricted cofactors .",
    "target_text": "B cell-specific transcriptional promoter activity mediated by the <DNA> octamer motif </DNA> requires the <protein> Oct1 </protein> or <protein> Oct2 protein </protein> and additional <protein> B cell-restricted cofactors </protein> ."
  },
  {
    "input_text": "One such cofactor , BOB.1/OBF.1 , was recently isolated from human B cells .",
    "target_text": "One such <protein> cofactor </protein> , <protein> BOB.1/OBF.1 </protein> , was recently isolated from <cell_type> human B cells </cell_type> ."
  },
  {
    "input_text": "Here , we describe the isolation and detailed characterization of the murine homolog .",
    "target_text": "Here , we describe the isolation and detailed characterization of the <protein> murine homolog </protein> ."
  },
  {
    "input_text": "Full-length cDNAs and genomic clones were isolated , and the gene structure was determined . Comparison of the deduced amino acids shows 88 % sequence identity between mouse and human BOB.1/OBF.1 .",
    "target_text": "Full-length <DNA> cDNAs </DNA> and <DNA> genomic clones </DNA> were isolated , and the gene structure was determined . Comparison of the deduced amino acids shows 88 % sequence identity between mouse and human BOB.1/OBF.1 ."
  },
  {
    "input_text": "The NH2-terminal 126 amino acids of BOB.1/OBF.1 are both essential and sufficient for interaction with the POU domains of either Oct1 or Oct2 .",
    "target_text": "The <protein> NH2-terminal 126 amino acids </protein> of <protein> BOB.1/OBF.1 </protein> are both essential and sufficient for interaction with the <protein> POU domains </protein> of either <protein> Oct1 </protein> or <protein> Oct2 </protein> ."
  },
  {
    "input_text": "This protein-protein interaction does not require the simultaneous binding of Oct proteins to DNA , and high resolution footprinting of the Oct -DNA interaction reveals that binding of BOB.1/OBF.1 to Oct1 or Oct2 does not alter the interaction with DNA .",
    "target_text": "This protein-protein interaction does not require the simultaneous binding of <protein> Oct proteins </protein> to DNA , and high resolution footprinting of the <DNA> Oct </DNA> -DNA interaction reveals that binding of <protein> BOB.1/OBF.1 </protein> to <protein> Oct1 </protein> or <protein> Oct2 </protein> does not alter the interaction with DNA ."
  },
  {
    "input_text": "BOB.1/OBF.1 can efficiently activate octamer-dependent promoters in fibroblasts ; however , it fails to stimulate octamer-dependent enhancer activity .",
    "target_text": "<protein> BOB.1/OBF.1 </protein> can efficiently activate octamer-dependent promoters in <cell_type> fibroblasts </cell_type> ; however , it fails to stimulate <DNA> octamer-dependent enhancer </DNA> activity ."
  },
  {
    "input_text": "Fusion of subdomains of BOB.1/OBF.1 with the GAL4 DNA binding domain reveals that both NH2- and COOH- terminal domains of BOB.1/OBF.1 contribute to full transactivation function , the COOH-terminal domain is more efficient in this transactivation assay .",
    "target_text": "Fusion of subdomains of <protein> BOB.1/OBF.1 </protein> with the <protein> GAL4 DNA binding domain </protein> reveals that both NH2- and COOH- terminal domains of <protein> BOB.1/OBF.1 </protein> contribute to full transactivation function , the <protein> COOH-terminal domain </protein> is more efficient in this transactivation assay ."
  },
  {
    "input_text": "Consistent with the failure of full-length BOB.1/OBF.1 to stimulate octamer-dependent enhancer elements in non B cells , the GAL4 fusions likewise only stimulate from a promoter-proximal position .",
    "target_text": "Consistent with the failure of <protein> full-length <protein> BOB.1/OBF.1 </protein> </protein> to stimulate <DNA> octamer-dependent enhancer elements </DNA> in <cell_type> non B cells </cell_type> , the <protein> GAL4 fusions </protein> likewise only stimulate from a promoter-proximal position ."
  },
  {
    "input_text": "Anti-immunoglobulin M activates nuclear calcium /calmodulin-dependent protein kinase II in human B lymphocytes .",
    "target_text": "<protein> Anti-immunoglobulin M </protein> activates <protein> nuclear calcium /calmodulin-dependent protein kinase II </protein> in <cell_type> human B lymphocytes </cell_type> ."
  },
  {
    "input_text": "We and others have previously shown that the nuclear protein , Ets-1 , is phosphorylated in a calcium-dependent manner after ligation of immunoglobulin ( Ig ) M on B lymphocytes .",
    "target_text": "We and others have previously shown that the <protein> nuclear protein </protein> , <protein> Ets-1 </protein> , is phosphorylated in a calcium-dependent manner after ligation of <protein> immunoglobulin ( Ig ) M </protein> on <cell_type> B lymphocytes </cell_type> ."
  },
  {
    "input_text": "As this phosphorylation was independent of protein kinase C activity , we tested whether a calcium /calmodulin-dependent protein kinase ( CaM kinase ) might phosphorylate the Ets-1 protein after elevation of intracellular free calcium concentrations .",
    "target_text": "As this phosphorylation was independent of <protein> protein kinase C </protein> activity , we tested whether a <protein> calcium /calmodulin-dependent protein kinase </protein> ( <protein> CaM kinase </protein> ) might phosphorylate the <protein> <protein> Ets-1 </protein> protein </protein> after elevation of intracellular free calcium concentrations ."
  },
  {
    "input_text": "The dephosphorylated form of Ets-1 has been shown to bind to chromatin , suggesting that the operative kinase should be detectable in the nucleus .",
    "target_text": "The dephosphorylated form of <protein> Ets-1 </protein> has been shown to bind to <DNA> chromatin </DNA> , suggesting that the <protein> operative kinase </protein> should be detectable in the nucleus ."
  },
  {
    "input_text": "We prepared nuclear extracts from two human B cell lines in which increased intracellular free calcium levels correlated with increased phosphorylation of the Ets-1 protein .",
    "target_text": "We prepared nuclear extracts from two <cell_line> human B cell lines </cell_line> in which increased intracellular free calcium levels correlated with increased phosphorylation of the <protein> Ets-1 </protein> protein ."
  },
  {
    "input_text": "Activity of the CaM kinases was determined using a synthetic peptide substrate both in the absence and presence of an inhibitor specific for the CaM kinase family , KN-62 .",
    "target_text": "Activity of the <protein> CaM kinases </protein> was determined using a synthetic peptide substrate both in the absence and presence of an inhibitor specific for the <protein> <protein> CaM kinase </protein> family </protein> , KN-62 ."
  },
  {
    "input_text": "Stimulation of cells with anti-IgM led to increased activity of a nuclear kinase that could phosphorylate the peptide , and this activity was reduced by 10 microM KN-62 .",
    "target_text": "Stimulation of cells with <protein> anti-IgM </protein> led to increased activity of a <protein> nuclear kinase </protein> that could phosphorylate the peptide , and this activity was reduced by 10 microM KN-62 ."
  },
  {
    "input_text": "Kinase activity was reduced in lysates preadsorbed using an antibody specific for CaM kinase II .",
    "target_text": "Kinase activity was reduced in lysates preadsorbed using an <protein> antibody </protein> specific for <protein> CaM kinase II </protein> ."
  },
  {
    "input_text": "Two-dimensional phosphopeptide maps of the Ets-1 protein from cells incubated with ionomycin or anti-IgM contained two unique phosphopeptides that were absent in untreated cells .",
    "target_text": "Two-dimensional phosphopeptide maps of the <protein> Ets-1 </protein> protein from cells incubated with ionomycin or <protein> anti-IgM </protein> contained two unique phosphopeptides that were absent in untreated cells ."
  },
  {
    "input_text": "Incubation of isolated Ets-1 protein with purified CaM kinase II produced phosphorylation of peptides that migrated identically to those found in cells incubated with either anti-IgM or ionomycin .",
    "target_text": "Incubation of <protein> isolated Ets-1 protein </protein> with purified <protein> CaM kinase II </protein> produced phosphorylation of peptides that migrated identically to those found in cells incubated with either <protein> anti-IgM </protein> or ionomycin ."
  },
  {
    "input_text": "These data suggest a model of signal transduction by the antigen receptor on B lymphocytes in which increased intracellular free calcium can rapidly activate nuclear CaM kinase II , potentially resulting in phosphorylation and regulation of DNA-binding proteins .",
    "target_text": "These data suggest a model of signal transduction by the <protein> antigen receptor </protein> on <cell_type> B lymphocytes </cell_type> in which increased intracellular free calcium can rapidly activate <protein> nuclear CaM kinase II </protein> , potentially resulting in phosphorylation and regulation of <protein> DNA-binding proteins </protein> ."
  },
  {
    "input_text": "Transcriptional activation and repression , two properties of the lymphoid-specific transcription factor Oct-2a .",
    "target_text": "Transcriptional activation and repression , two properties of the <protein> lymphoid-specific transcription factor </protein> <protein> Oct-2a </protein> ."
  },
  {
    "input_text": "The lymphoid-specific transcription factor Oct-2a contains two transcriptional activation domains which are located within the N-terminal and C-terminal regions .",
    "target_text": "The <protein> lymphoid-specific transcription factor </protein> <protein> Oct-2a </protein> contains two <protein> transcriptional activation domains </protein> which are located within the <protein> N-terminal </protein> and <protein> C-terminal regions </protein> ."
  },
  {
    "input_text": "To study their differential activation properties , we linked the isolated effector domains to the GAL4 DNA-binding domain .",
    "target_text": "To study their <protein> differential activation properties </protein> , we linked the isolated <protein> effector domains </protein> to the <protein> GAL4 DNA-binding domain </protein> ."
  },
  {
    "input_text": "We have shown that both activating regions of Oct-2a , isolated from their natural context , can activate transcription as promoter factors .",
    "target_text": "We have shown that both activating regions of <protein> Oct-2a </protein> , isolated from their natural context , can activate transcription as <protein> promoter factors </protein> ."
  },
  {
    "input_text": "In contrast to the C-terminus , activation by the N-terminal domain is dependent on a yet unidentified factor ( s ) binding to the simian virus 40 enhancer .",
    "target_text": "In contrast to the <protein> C-terminus </protein> , activation by the <protein> N-terminal domain </protein> is dependent on a yet unidentified factor ( s ) binding to the <DNA> simian virus 40 enhancer </DNA> ."
  },
  {
    "input_text": "The results obtained by duplication of activation domains or their mixed combination suggest that the domains are functionally independent .",
    "target_text": "The results obtained by duplication of <protein> activation domains </protein> or their mixed combination suggest that the domains are functionally independent ."
  },
  {
    "input_text": "However , activation from a remote position could only be achieved with the C-terminus of Oct-2a in B cells .",
    "target_text": "However , activation from a remote position could only be achieved with the <protein> C-terminus </protein> of <protein> Oct-2a </protein> in <cell_type> B cells </cell_type> ."
  },
  {
    "input_text": "In lymphoid cells , higher activation levels were observed , suggesting that distinct B-cell-specific cofactors in concert with the effector domains of Oct-2a might be involved in mediating transcription from proximal and remote positions .",
    "target_text": "In <cell_type> lymphoid cells </cell_type> , higher activation levels were observed , suggesting that distinct <protein> B-cell-specific cofactors </protein> in concert with the <protein> effector domains </protein> of <protein> Oct-2a </protein> might be involved in mediating transcription from proximal and remote positions ."
  },
  {
    "input_text": "Furthermore , we identified a repression domain at the N-terminus of Oct-2a .",
    "target_text": "Furthermore , we identified a repression domain at the N-terminus of <protein> Oct-2a </protein> ."
  },
  {
    "input_text": "When transferred to a potent activator , transcriptional stimulation was inhibited efficiently .",
    "target_text": "When transferred to a potent activator , transcriptional stimulation was inhibited efficiently ."
  },
  {
    "input_text": "These results underscore the modular structure of Oct-2a with separable domains for activation and repression and suggest that Oct-2a might have complex regulatory functions in vivo .",
    "target_text": "These results underscore the modular structure of <protein> Oct-2a </protein> with separable domains for activation and repression and suggest that <protein> Oct-2a </protein> might have complex regulatory functions in vivo ."
  },
  {
    "input_text": "Nonopsonic phagocytosis of Pseudomonas aeruginosa by macrophages and polymorphonuclear leukocytes requires the presence of the bacterial flagellum .",
    "target_text": "Nonopsonic phagocytosis of Pseudomonas aeruginosa by <cell_type> macrophages </cell_type> and <cell_type> polymorphonuclear leukocytes </cell_type> requires the presence of the bacterial flagellum ."
  },
  {
    "input_text": "Whereas the mechanism of nonopsonic phagocytosis of Pseudomonas aeruginosa has been described , the bacterial ligands required are poorly understood .",
    "target_text": "Whereas the mechanism of nonopsonic phagocytosis of Pseudomonas aeruginosa has been described , the bacterial ligands required are poorly understood ."
  },
  {
    "input_text": "To identify the requisite bacterial ligands , studies with isogenic mutants of P. aeruginosa PAK lacking pili , flagella , and the RpoN sigma factor were undertaken .",
    "target_text": "To identify the requisite bacterial ligands , studies with isogenic mutants of P. aeruginosa PAK lacking pili , flagella , and the <protein> RpoN sigma factor </protein> were undertaken ."
  },
  {
    "input_text": "The RpoN mutant , lacking pili , flagella , and nonpilus adhesins , bound poorly and was resistant to ingestion by both macrophages and neutrophils .",
    "target_text": "The RpoN mutant , lacking pili , flagella , and <protein> nonpilus adhesins </protein> , bound poorly and was resistant to ingestion by both <cell_type> macrophages </cell_type> and <cell_type> neutrophils </cell_type> ."
  },
  {
    "input_text": "Pili were not absolutely required for binding or phagocytosis of P. aeruginosa .",
    "target_text": "Pili were not absolutely required for binding or phagocytosis of P. aeruginosa ."
  },
  {
    "input_text": "The presence of a flagellum was not required for binding of P. aeruginosa to macrophages but was critical for the subsequent internalization of the bacterium , suggesting that this factor or a surface ligand associated with its assembly was responsible for stimulation of nonopsonic phagocytosis .",
    "target_text": "The presence of a flagellum was not required for binding of P. aeruginosa to <cell_type> macrophages </cell_type> but was critical for the subsequent internalization of the bacterium , suggesting that this factor or a surface ligand associated with its assembly was responsible for stimulation of nonopsonic phagocytosis ."
  },
  {
    "input_text": "Identification of essential GATA and Ets binding motifs within the promoter of the platelet glycoprotein Ib alpha gene .",
    "target_text": "Identification of essential <DNA> GATA </DNA> and <DNA> Ets binding motifs </DNA> within the promoter of the <DNA> platelet glycoprotein Ib alpha gene </DNA> ."
  },
  {
    "input_text": "Platelet glycoprotein ( GP ) Ib-IX-V is a multisubunit adhesion receptor that supports platelet attachment to thrombogenic surfaces at sites of vascular injury .",
    "target_text": "<protein> Platelet glycoprotein </protein> ( <protein> GP </protein> ) <protein> Ib-IX-V </protein> is a <protein> multisubunit adhesion receptor </protein> that supports platelet attachment to thrombogenic surfaces at sites of vascular injury ."
  },
  {
    "input_text": "The congenital absence of the receptor results in a bleeding disorder associated with \" giant \" platelets , a condition linking the expression of the complex to platelet morphogenesis .",
    "target_text": "The congenital absence of the receptor results in a bleeding disorder associated with <cell_type> \" giant \" platelets </cell_type> , a condition linking the expression of the complex to platelet morphogenesis ."
  },
  {
    "input_text": "To understand better the expression of the GP Ib-IX-V complex , studies were undertaken to define the essential genetic elements supporting the expression of the alpha-subunit of the complex ( GP Ib alpha ) .",
    "target_text": "To understand better the expression of the <protein> <protein> GP </protein> <protein> Ib-IX-V </protein> complex </protein> , studies were undertaken to define the essential <DNA> genetic elements </DNA> supporting the expression of the <protein> alpha-subunit </protein> of the complex ( <protein> <protein> GP </protein> Ib alpha </protein> ) ."
  },
  {
    "input_text": "GP Ib alpha promoter activity was evaluated by transfection of human erythroleukemia cells with reporter plasmids coding for the enzyme , luciferase .",
    "target_text": "<DNA> <protein> GP </protein> Ib alpha promoter </DNA> activity was evaluated by transfection of <cell_type> human erythroleukemia cells </cell_type> with reporter plasmids coding for the <protein> enzyme </protein> , <protein> luciferase </protein> ."
  },
  {
    "input_text": "Studies were initiated with a fragment extending 2,738 nucleotides 5' to the transcription start site and lead to the identification of 253 nucleotides retaining full promoter activity in human erythroleukemia cells .",
    "target_text": "Studies were initiated with a fragment extending 2,738 nucleotides 5' to the <DNA> transcription start site </DNA> and lead to the identification of 253 nucleotides retaining full promoter activity in <cell_type> human erythroleukemia cells </cell_type> ."
  },
  {
    "input_text": "In cells of nonhematopoietic lineage , human endothelial and HeLa cells , the GP Ib alpha promoter activity was no greater than background levels obtained with promoterless constructs .",
    "target_text": "In cells of <cell_type> nonhematopoietic lineage </cell_type> , <cell_type> human endothelial </cell_type> and <cell_type> HeLa cells </cell_type> , the <DNA> <protein> <protein> GP </protein> Ib alpha </protein> promoter </DNA> activity was no greater than background levels obtained with <DNA> promoterless constructs </DNA> ."
  },
  {
    "input_text": "Gel shift assays and site-directed mutagenesis studies defined essential GATA and Ets binding motifs 93 and 150 nucleotides upstream of the transcription start site , a finding which further substantiates these elements as important determinants of megakaryocytic gene expression .",
    "target_text": "Gel shift assays and site-directed mutagenesis studies defined essential <DNA> GATA </DNA> and <DNA> Ets binding motifs </DNA> <DNA> 93 and 150 nucleotides upstream </DNA> of the <DNA> transcription start site </DNA> , a finding which further substantiates these elements as important determinants of megakaryocytic gene expression ."
  },
  {
    "input_text": "The results define essential cis-acting elements responsible for the expression of GP Ib alpha and provide insights into molecular events coinciding with the release of normal platelets into the bloodstream .",
    "target_text": "The results define essential <DNA> cis-acting elements </DNA> responsible for the expression of <protein> <protein> GP </protein> Ib alpha </protein> and provide insights into molecular events coinciding with the release of <cell_type> normal platelets </cell_type> into the bloodstream ."
  },
  {
    "input_text": "CD30 ligation induces nuclear factor-kappa B activation in human T cell lines .",
    "target_text": "<protein> CD30 </protein> ligation induces <protein> nuclear factor-kappa B </protein> activation in <cell_line> human T cell lines </cell_line> ."
  },
  {
    "input_text": "CD30 is a recently described member of the tumor necrosis factor /nerve growth factor receptor superfamily .",
    "target_text": "<protein> CD30 </protein> is a recently described member of the <protein> <protein> tumor necrosis factor </protein> <protein> /nerve growth factor </protein> receptor superfamily </protein> ."
  },
  {
    "input_text": "In this report , we show that following incubation of L540 cells ( Hodgkin 's disease -derived , T cell-like , CD30 + cells ) with the agonistic anti- CD30 monoclonal antibodies ( mAb ) M44 and M67 , two nuclear factor ( NF ) -kappa B DNA binding activities were induced in nuclear extracts , as determined in gel retardation assays .",
    "target_text": "In this report , we show that following incubation of <cell_line> L540 cells </cell_line> ( <cell_line> Hodgkin 's disease -derived , T cell-like , <protein> CD30 </protein> + cells </cell_line> ) with the <protein> agonistic anti- <protein> CD30 </protein> monoclonal antibodies </protein> ( <protein> mAb </protein> ) <protein> M44 </protein> and <protein> M67 </protein> , two <protein> nuclear factor ( NF ) -kappa B </protein> DNA binding activities were induced in nuclear extracts , as determined in gel retardation assays ."
  },
  {
    "input_text": "The effect of the mAb towards NF-kappa B activation was rapid , as it occurred within 20 min , and was sustained for up to 6 h .",
    "target_text": "The effect of the <protein> mAb </protein> towards <protein> NF-kappa B </protein> activation was rapid , as it occurred within 20 min , and was sustained for up to 6 h ."
  },
  {
    "input_text": "By comparison , an isotype-matched antibody had no effect on NF-kappa B activation .",
    "target_text": "By comparison , an <protein> isotype-matched antibody </protein> had no effect on <protein> NF-kappa B </protein> activation ."
  },
  {
    "input_text": "Moreover , in human T helper ( Th ) clones functionally characterized as being of the type 0 , type 1 and type 2 ( 28 % , < 1 % und 93 % CD30+ , respectively ) , the extent of CD30 -mediated NF-kappa B activation correlated with the proportion of CD30+ cells .",
    "target_text": "Moreover , in <cell_line> human T helper ( Th ) clones </cell_line> functionally characterized as being of the type 0 , type 1 and type 2 ( 28 % , < 1 % und 93 % CD30+ , respectively ) , the extent of <protein> CD30 </protein> -mediated <protein> NF-kappa B </protein> activation correlated with the proportion of <cell_line> CD30+ cells </cell_line> ."
  },
  {
    "input_text": "In all cell lines investigated , the NF-kappa B complexes induced following CD30 engagement were shown to contain p50 NF-kappa B1 , p65 RelA , and possibly other transcription factors .",
    "target_text": "In all cell lines investigated , the <protein> <protein> NF-kappa B </protein> complexes </protein> induced following <protein> CD30 </protein> engagement were shown to contain <protein> p50 NF-kappa B1 </protein> , <protein> p65 RelA </protein> , and possibly other <protein> transcription factors </protein> ."
  },
  {
    "input_text": "Collectively , our results demonstrate that nuclear translocation and activation of NF-kappa B rank among the short-term cellular responses elicited following CD30 ligation .",
    "target_text": "Collectively , our results demonstrate that nuclear translocation and activation of <protein> NF-kappa B </protein> rank among the short-term cellular responses elicited following <protein> CD30 </protein> ligation ."
  },
  {
    "input_text": "Pathogenesis of atherosclerosis .",
    "target_text": "Pathogenesis of atherosclerosis ."
  },
  {
    "input_text": "The earliest lesion in the development of an atherosclerotic plaque is the fatty streak .",
    "target_text": "The earliest lesion in the development of an atherosclerotic plaque is the fatty streak ."
  },
  {
    "input_text": "This chronic inflammatory reaction results from a sequence of events that begins with the trapping of low density lipoprotein ( LDL ) in the subendothelial space of the artery wall .",
    "target_text": "This chronic inflammatory reaction results from a sequence of events that begins with the trapping of low density lipoprotein ( LDL ) in the subendothelial space of the artery wall ."
  },
  {
    "input_text": "The trapped LDL is seeded with oxidative species released by the overlying endothelium , and lipid oxidation is initiated within the LDL particle . Some of the lipids that result lead to the activation of NFkB-like transcription factors that cause the expression of genes whose protein products mediate monocyte binding , monocyte chemotaxis into the subendothelial space , and conversion into macrophages .",
    "target_text": "The trapped LDL is seeded with oxidative species released by the overlying endothelium , and lipid oxidation is initiated within the LDL particle . Some of the lipids that result lead to the activation of <protein> NFkB-like <protein> transcription factors </protein> </protein> that cause the expression of genes whose <protein> protein products </protein> mediate monocyte binding , <cell_type> monocyte </cell_type> chemotaxis into the subendothelial space , and conversion into <cell_type> macrophages </cell_type> ."
  },
  {
    "input_text": "At least 1 major gene modulates the oxidation of LDL lipids and/or the biologic response to these lipids .",
    "target_text": "At least 1 <DNA> major gene </DNA> modulates the oxidation of LDL lipids and/or the biologic response to these lipids ."
  },
  {
    "input_text": "The inverse relation between high density lipoprotein ( HDL ) and atherosclerotic events may in part be due to enzymes associated with HDL that destroy the biologically active lipids generated in LDL .",
    "target_text": "The inverse relation between high density lipoprotein ( HDL ) and atherosclerotic events may in part be due to <protein> enzymes </protein> associated with HDL that destroy the biologically active lipids generated in LDL ."
  },
  {
    "input_text": "Estrogen and progesterone receptors in vernal keratoconjunctivitis .",
    "target_text": "<protein> Estrogen </protein> and <protein> progesterone receptors </protein> in vernal keratoconjunctivitis ."
  },
  {
    "input_text": "PURPOSE : Sex-related influences have been implicated in the pathogenesis of vernal keratoconjunctivitis ( VKC ) , an allergic eosinophilic disease .",
    "target_text": "PURPOSE : Sex-related influences have been implicated in the pathogenesis of vernal keratoconjunctivitis ( VKC ) , an allergic eosinophilic disease ."
  },
  {
    "input_text": "METHODS : The authors evaluated tarsal and bulbar conjunctival biopsies from seven patients with severe and symptomatic VKC for the presence of estrogen and progesterone receptors by using monoclonal antibodies with a peroxidase-antiperoxidase technique .",
    "target_text": "METHODS : The authors evaluated tarsal and bulbar conjunctival biopsies from seven patients with severe and symptomatic VKC for the presence of <protein> estrogen </protein> and <protein> progesterone receptors </protein> by using <protein> monoclonal antibodies </protein> with a peroxidase-antiperoxidase technique ."
  },
  {
    "input_text": "RESULTS : Both the epithelium and subepithelium of the tarsal and bulbar conjunctiva of patients with VKC , but not those of four nonatopic control subjects , showed intense positive staining for estrogen and progesterone receptors .",
    "target_text": "RESULTS : Both the epithelium and subepithelium of the tarsal and bulbar conjunctiva of patients with VKC , but not those of four nonatopic control subjects , showed intense positive staining for estrogen and <protein> progesterone receptors </protein> ."
  },
  {
    "input_text": "Immunofluorescence colocalization of both estrogen and progesterone receptors with eosinophil cationic protein showed that approximately 70 % of positive cells were eosinophils .",
    "target_text": "Immunofluorescence colocalization of both <protein> estrogen </protein> and <protein> progesterone receptors </protein> with <protein> eosinophil cationic protein </protein> showed that approximately 70 % of <cell_type> positive cells </cell_type> were <cell_type> eosinophils </cell_type> ."
  },
  {
    "input_text": "CONCLUSIONS : Sexual hormones , through their receptors , may influence the activity of eosinophils in patients with VKC .",
    "target_text": "CONCLUSIONS : Sexual hormones , through their <protein> receptors </protein> , may influence the activity of <cell_type> eosinophils </cell_type> in patients with VKC ."
  },
  {
    "input_text": "CIITA activates the expression of MHC class II genes in mouse T cells .",
    "target_text": "<protein> CIITA </protein> activates the expression of <DNA> MHC class II genes </DNA> in mouse T cells ."
  },
  {
    "input_text": "It has long been a puzzle that MHC class II molecules are expressed in human T cells after activation but not in mouse T cells ; this expression is believed to play a role in the cell mediated immune response .",
    "target_text": "It has long been a puzzle that <protein> MHC class II molecules </protein> are expressed in <cell_type> human T cells </cell_type> after activation but not in <cell_type> mouse T cells </cell_type> ; this expression is believed to play a role in the cell mediated immune response ."
  },
  {
    "input_text": "Recently the MHC class II transactivator ( CIITA ) has been reported to be a major regulatory factor for both the constitutive and IFN inducible expression of MHC class II genes .",
    "target_text": "Recently the <protein> MHC class II transactivator </protein> ( <protein> CIITA </protein> ) has been reported to be a <protein> major regulatory factor </protein> for both the constitutive and IFN inducible expression of <DNA> MHC class II genes </DNA> ."
  },
  {
    "input_text": "Here we show that human T cells expressing MHC class II have CIITA transcripts while MHC class II-negative human T cells and mouse T cells do not .",
    "target_text": "Here we show that <cell_type> human T cells </cell_type> expressing MHC class II have <protein> CIITA </protein> transcripts while MHC class II-negative <cell_type> human T cells </cell_type> and <cell_type> mouse T cells </cell_type> do not ."
  },
  {
    "input_text": "The expression of MHC class II genes in mouse T cells can be reconstituted upon transfection with the human CIITA cDNA .",
    "target_text": "The expression of <DNA> MHC class II genes </DNA> in <cell_type> mouse T cells </cell_type> can be reconstituted upon transfection with the <DNA> human <protein> CIITA </protein> cDNA </DNA> ."
  },
  {
    "input_text": "These data indicate that the expression of CIITA explains the expression or lack of expression of MHC class II in human and mouse T cells respectively .",
    "target_text": "These data indicate that the expression of <protein> CIITA </protein> explains the expression or lack of expression of <protein> MHC class II </protein> in <cell_type> human </cell_type> and <cell_type> mouse T cells </cell_type> respectively ."
  },
  {
    "input_text": "Anti-Ro(SSA) autoantibodies are associated with T cell receptor beta genes in systemic lupus erythematosus patients .",
    "target_text": "<protein> Anti-Ro(SSA) autoantibodies </protein> are associated with <DNA> T cell receptor beta genes </DNA> in systemic lupus erythematosus patients ."
  },
  {
    "input_text": "Several of the heterogeneous clinical manifestations of systemic lupus erythematosus have been associated with specific autoantibodies .",
    "target_text": "Several of the heterogeneous clinical manifestations of systemic lupus erythematosus have been associated with specific <protein> autoantibodies </protein> ."
  },
  {
    "input_text": "Associations between HLA class II antigens and autoantibodies to the ribonucleoproteins Ro(SSA) and La(SSB) have been reported in these patients .",
    "target_text": "Associations between <protein> HLA class II antigens </protein> and <protein> autoantibodies </protein> to the <protein> ribonucleoproteins </protein> <protein> Ro(SSA) </protein> and <protein> La(SSB) </protein> have been reported in these patients ."
  },
  {
    "input_text": "Because HLA class II molecules present antigen to T cell receptors ( TCRs ) , we have searched for a TCR gene associated with the production of anti- Ro(SSA) antibodies .",
    "target_text": "Because <protein> HLA class II molecules </protein> present antigen to <protein> T cell receptors </protein> ( <protein> TCRs </protein> ) , we have searched for a <DNA> TCR gene </DNA> associated with the production of <protein> anti- <protein> Ro(SSA) </protein> antibodies </protein> ."
  },
  {
    "input_text": "A pair of restriction fragment length polymorphisms ( RFLPs ) , one of which hybridizes to the TCR constant region C beta 1 and the other to the C beta 2 gene , has been identified , suggesting these may be genotypic markers for an extended region of the TCR beta locus .",
    "target_text": "A pair of <DNA> restriction fragment length polymorphisms </DNA> ( <DNA> RFLPs </DNA> ) , one of which hybridizes to the <DNA> TCR constant region C beta 1 </DNA> and the other to the <DNA> C beta 2 gene </DNA> , has been identified , suggesting these may be genotypic markers for an extended region of the <DNA> TCR beta locus </DNA> ."
  },
  {
    "input_text": "This RFLP pair occurs in 76 % of patients with Ro(SSA) precipitins , 84 % of anti- Ro(SSA) -positive patients lacking La(SSB) precipitins , but only 41 % of the patients lacking both precipitins ( P = 0.0004 ) .",
    "target_text": "This <DNA> RFLP pair </DNA> occurs in 76 % of patients with <protein> Ro(SSA) </protein> precipitins , 84 % of anti- <protein> Ro(SSA) </protein> -positive patients lacking <protein> La(SSB) </protein> <protein> precipitins </protein> , but only 41 % of the patients lacking both <protein> precipitins </protein> ( P = 0.0004 ) ."
  },
  {
    "input_text": "This disproportionate occurrence in a subset of lupus patients indicates that these RFLPs are not disease susceptibility markers , but rather are important markers for TCR genes whose products are involved in the production of anti- Ro(SSA) antibodies .",
    "target_text": "This disproportionate occurrence in a subset of lupus patients indicates that these <DNA> RFLPs </DNA> are not disease susceptibility markers , but rather are important markers for <DNA> TCR genes </DNA> whose products are involved in the production of <protein> anti- <protein> Ro(SSA) </protein> antibodies </protein> ."
  },
  {
    "input_text": "The majority of patients who have these RFLPs and HLA class II antigens previously associated with the anti- Ro(SSA) response make this antibody , suggesting that interactions between products of these loci occur in response to Ro(SSA) .",
    "target_text": "The majority of patients who have these <DNA> RFLPs </DNA> and <protein> HLA class II antigens </protein> previously associated with the anti- <protein> Ro(SSA) </protein> response make this antibody , suggesting that interactions between products of these <DNA> loci occur </DNA> in response to <protein> Ro(SSA) </protein> ."
  },
  {
    "input_text": "Inhibition of NF-AT -dependent transcription by NF-kappa B : implications for differential gene expression in T helper cell subsets .",
    "target_text": "Inhibition of <protein> NF-AT </protein> -dependent transcription by <protein> NF-kappa B </protein> : implications for differential gene expression in <cell_type> T helper cell subsets </cell_type> ."
  },
  {
    "input_text": "Activation of individual CD4+ T cells results in differential lymphokine expression : interleukin 2 ( IL-2 ) is preferentially produced by T helper type 1 ( TH1 ) cells , which are involved in cell-mediated immune responses , whereas IL-4 is synthesized by TH2 cells , which are essential for humoral immunity .",
    "target_text": "Activation of individual <cell_line> CD4+ T cells </cell_line> results in differential <protein> lymphokine </protein> expression : <protein> interleukin 2 </protein> ( <protein> IL-2 </protein> ) is preferentially produced by <cell_line> T helper type 1 ( TH1 ) cells </cell_line> , which are involved in cell-mediated immune responses , whereas <protein> IL-4 </protein> is synthesized by <cell_line> TH2 cells </cell_line> , which are essential for humoral immunity ."
  },
  {
    "input_text": "The Ca(2+) -dependent factor NF-ATp plays a key role in the inducible transcription of both these lymphokine genes .",
    "target_text": "The <protein> Ca(2+) -dependent factor </protein> <protein> NF-ATp </protein> plays a key role in the inducible transcription of both these <DNA> lymphokine genes </DNA> ."
  },
  {
    "input_text": "However , while IL2 expression requires the contribution of Ca(2+)- and protein kinase C -dependent signals , we report that activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells .",
    "target_text": "However , while <protein> IL2 </protein> expression requires the contribution of Ca(2+)- and <protein> protein kinase C </protein> -dependent signals , we report that activation of <protein> human IL4 </protein> transcription through the Ca(2+)-dependent pathway is diminished by <protein> protein kinase C </protein> stimulation in <cell_line> Jurkat T cells </cell_line> ."
  },
  {
    "input_text": "This phenomenon is due to mutually exclusive binding of NF-ATp and NF-kappa B to the P sequence , an element located 69 bp upstream of the IL4 transcription initiation site .",
    "target_text": "This phenomenon is due to mutually exclusive binding of <protein> NF-ATp </protein> and <protein> NF-kappa B </protein> to the <DNA> P sequence </DNA> , an element located <DNA> 69 bp upstream </DNA> of the <DNA> IL4 transcription initiation site </DNA> ."
  },
  {
    "input_text": "Human IL4 promoter -mediated transcription is downregulated in Jurkat cells stimulated with the NF-kappa B -activating cytokine tumor necrosis factor alpha and suppressed in RelA -overexpressing cells .",
    "target_text": "<DNA> Human IL4 promoter </DNA> -mediated transcription is downregulated in <cell_line> Jurkat cells </cell_line> stimulated with the <protein> <protein> NF-kappa B </protein> -activating cytokine </protein> <protein> tumor necrosis factor alpha </protein> and suppressed in <cell_line> <protein> RelA </protein> -overexpressing cells </cell_line> ."
  },
  {
    "input_text": "In contrast , protein kinase C stimulation or RelA overexpression does not affect the activity of a human IL4 promoter containing a mouse P sequence , which is a higher-affinity site for NF-ATp and a lower-affinity site for RelA .",
    "target_text": "In contrast , <protein> protein kinase C </protein> stimulation or <protein> RelA </protein> overexpression does not affect the activity of a <DNA> <protein> human IL4 </protein> promoter </DNA> containing a <DNA> mouse <DNA> P sequence </DNA> </DNA> , which is a <DNA> higher-affinity site </DNA> for <protein> NF-ATp </protein> and a <DNA> lower-affinity site </DNA> for <protein> RelA </protein> ."
  },
  {
    "input_text": "Thus , competition between two general transcriptional activators , RelA and NF-ATp , mediates the inhibitory effect of protein kinase C stimulation on IL4 expression and may contribute to differential gene expression in TH cells .",
    "target_text": "Thus , competition between two general <protein> transcriptional activators </protein> , <protein> RelA </protein> and <protein> NF-ATp </protein> , mediates the inhibitory effect of <protein> protein kinase C </protein> stimulation on <protein> IL4 </protein> expression and may contribute to differential gene expression in <cell_line> TH cells </cell_line> ."
  },
  {
    "input_text": "Regulation of the balance of cytokine production and the signal transducer and activator of transcription ( STAT ) transcription factor activity by cytokines and inflammatory synovial fluids .",
    "target_text": "Regulation of the balance of <protein> cytokine </protein> production and the signal transducer and activator of transcription ( <protein> STAT </protein> ) transcription factor activity by <protein> cytokines </protein> and inflammatory synovial fluids ."
  },
  {
    "input_text": "The balance between type 1 and 2 T helper cell cytokine production plays an important role in several animal models of autoimmunity , and skewed patterns of cytokine expression have been described in human inflammatory diseases .",
    "target_text": "The balance between type 1 and 2 T helper cell cytokine production plays an important role in several animal models of autoimmunity , and skewed patterns of <protein> cytokine </protein> expression have been described in human inflammatory diseases ."
  },
  {
    "input_text": "Many cytokines activate signal transducer and activation of transcription ( STAT ) transcription factors , which , in turn , activate transcription of inflammatory effector genes .",
    "target_text": "Many <protein> cytokines </protein> activate <protein> signal transducer and activation of transcription ( <protein> STAT </protein> ) transcription factors </protein> , which , in turn , activate transcription of inflammatory effector genes ."
  },
  {
    "input_text": "We used mononuclear cell priming cultures and inflammatory synovial fluids ( SFs ) derived from arthritis patients to examine the regulation of cytokine production and STAT activity by an inflammatory synovial microenvironment .",
    "target_text": "We used <cell_line> mononuclear cell priming cultures </cell_line> and <cell_type> inflammatory synovial fluids </cell_type> ( <cell_type> SFs </cell_type> ) derived from arthritis patients to examine the regulation of <protein> cytokine </protein> production and <protein> STAT </protein> activity by an inflammatory synovial microenvironment ."
  },
  {
    "input_text": "Exposure to SFs during priming resulted in an 81 % inhibition of interferon ( IFN ) -gamma , but not interleukin ( IL ) 4 , production by effector cells generated in priming cultures .",
    "target_text": "Exposure to <cell_type> SFs </cell_type> during priming resulted in an 81 % inhibition of <protein> interferon ( IFN ) -gamma </protein> , but not <protein> interleukin ( IL ) 4 </protein> , production by <cell_type> effector cells </cell_type> generated in priming cultures ."
  },
  {
    "input_text": "SF suppression was mediated by IL-4 and IL-10 and inhibition of IL-12 expression , and it was reversed in a dominant fashion by exogenous IL-12 .",
    "target_text": "SF suppression was mediated by <protein> IL-4 </protein> and <protein> IL-10 </protein> and inhibition of <protein> IL-12 </protein> expression , and it was reversed in a dominant fashion by exogenous IL-12 ."
  },
  {
    "input_text": "SFs blocked the sustained activity of transcription factor Stat1 , but not Stat3 , during the priming period , and Stat1 activity was differentially regulated by cytokines in parallel with their positive or negative regulation of IFN-gamma production .",
    "target_text": "<cell_type> SFs </cell_type> blocked the sustained activity of <protein> transcription factor Stat1 </protein> , but not <protein> Stat3 </protein> , during the priming period , and <protein> Stat1 </protein> activity was differentially regulated by <protein> cytokines </protein> in parallel with their positive or negative regulation of <protein> IFN-gamma </protein> production ."
  },
  {
    "input_text": "Active Stat3 , but not Stat1 , was detected in cells from inflamed joints .",
    "target_text": "Active <protein> Stat3 </protein> , but not <protein> Stat1 </protein> , was detected in cells from inflamed joints ."
  },
  {
    "input_text": "These results suggest a role for altered balance of Stat1 and Stat3 transcriptional activity in the regulation of T cell differentiation and in the pathogenesis of inflammatory synovitis .",
    "target_text": "These results suggest a role for altered balance of Stat1 and Stat3 transcriptional activity in the regulation of <cell_type> T cell </cell_type> differentiation and in the pathogenesis of inflammatory synovitis ."
  },
  {
    "input_text": "Triggering of complement receptors CR1 ( CD35 ) and CR3 ( CD11b/CD18 ) induces nuclear translocation of NF-kappa B ( p50 /p65 ) in human monocytes and enhances viral replication in HIV-infected monocytic cells .",
    "target_text": "Triggering of <protein> complement receptors </protein> <protein> CR1 </protein> ( <protein> CD35 </protein> ) and <protein> CR3 </protein> ( <protein> CD11b/CD18 </protein> ) induces nuclear translocation of <protein> NF-kappa B </protein> ( <protein> p50 /p65 </protein> ) in <cell_type> human monocytes </cell_type> and enhances viral replication in <cell_type> HIV-infected monocytic cells </cell_type> ."
  },
  {
    "input_text": "Monocyte/macrophages may harbor HIV in a nonproductive fashion for prolonged periods of time .",
    "target_text": "<cell_type> Monocyte/macrophages </cell_type> may harbor HIV in a nonproductive fashion for prolonged periods of time ."
  },
  {
    "input_text": "Viral gene expression may be reactivated by stimulation of the cells with LPS or cytokines such as TNF-alpha in vitro .",
    "target_text": "Viral gene expression may be reactivated by stimulation of the cells with LPS or <protein> cytokines </protein> such as <protein> TNF-alpha </protein> in vitro ."
  },
  {
    "input_text": "The effect of LPS and TNF-alpha is mediated by their ability to induce nuclear translocation of the DNA-binding heterodimer NF-kappa B ( p50 /p65 ) , which binds to a specific sequence in the HIV-long terminal repeat .",
    "target_text": "The effect of LPS and <protein> TNF-alpha </protein> is mediated by their ability to induce nuclear translocation of the <protein> DNA-binding heterodimer </protein> <protein> NF-kappa B </protein> ( <protein> p50 /p65 </protein> ) , which binds to a specific sequence in the <DNA> HIV-long terminal repeat </DNA> ."
  },
  {
    "input_text": "The present study demonstrates that triggering of complement receptors CR1 ( CD35 ) and CR3 ( CD11b/CD18 ) enhances viral replication in HIV-infected human monocytic cells .",
    "target_text": "The present study demonstrates that triggering of <protein> complement receptors </protein> <protein> CR1 </protein> ( <protein> CD35 </protein> ) and <protein> CR3 </protein> ( <protein> CD11b/CD18 </protein> ) enhances viral replication in <cell_line> HIV-infected human monocytic cells </cell_line> ."
  },
  {
    "input_text": "Monocytic cell lines and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of F(ab')2 fragments of monoclonal anti- CR1 or anti- CR3 Abs or with C3 fragments .",
    "target_text": "<cell_line> Monocytic cell lines </cell_line> and normal peripheral blood monocytes were infected with HIV-1 in vitro and cultured in the presence or absence of <protein> F(ab')2 fragments </protein> of <protein> monoclonal anti- <protein> CR1 </protein> </protein> or <protein> anti- <protein> CR3 </protein> Abs </protein> or with <protein> C3 fragments </protein> ."
  },
  {
    "input_text": "Stimulation of CR1 or CR3 induces a two- to fourfold increase in the amount of cell-associated and released p24 Ag in cell cultures that was equivalent to that observed in control cultures triggered with LPS .",
    "target_text": "Stimulation of <protein> CR1 </protein> or <protein> CR3 </protein> induces a two- to fourfold increase in the amount of cell-associated and released <protein> p24 Ag </protein> in <cell_line> cell cultures </cell_line> that was equivalent to that observed in <cell_line> control cultures </cell_line> triggered with LPS ."
  },
  {
    "input_text": "We further observed that stimulation of CR1 or CR3 induces the nuclear translocation of NF-kappa B p50 /p65 in infected cells .",
    "target_text": "We further observed that stimulation of <protein> CR1 </protein> or <protein> CR3 </protein> induces the nuclear translocation of <protein> NF-kappa B </protein> <protein> p50 /p65 </protein> in <cell_type> infected cells </cell_type> ."
  },
  {
    "input_text": "Translocation of NF-kappa B p50 /p65 was also observed following stimulation of CR1 or CR3 of uninfected peripheral blood monocytes from HIV-seronegative donors .",
    "target_text": "Translocation of <protein> NF-kappa B </protein> <protein> p50 /p65 </protein> was also observed following stimulation of <protein> CR1 </protein> or <protein> CR3 </protein> of <cell_type> uninfected peripheral blood monocytes </cell_type> from HIV-seronegative donors ."
  },
  {
    "input_text": "The amount of protein translocated was similar to that observed when cells were stimulated with rhTNF-alpha .",
    "target_text": "The amount of protein translocated was similar to that observed when cells were stimulated with <protein> rhTNF-alpha </protein> ."
  },
  {
    "input_text": "TNF-alpha did not mediate the translocation of NF-kappa B p50 /p65 induced by triggering of complement receptors .",
    "target_text": "<protein> TNF-alpha </protein> did not mediate the translocation of <protein> NF-kappa B </protein> <protein> p50 /p65 </protein> induced by triggering of <protein> complement receptors </protein> ."
  },
  {
    "input_text": "Taken together , these observations suggest that HIV gene expression may be activated in infected monocytes through interaction of the cells with complement-opsonized particles and that enhanced viral replication is associated with C3 receptor -mediated nuclear translocation of the NF-kappa B complex .",
    "target_text": "Taken together , these observations suggest that HIV gene expression may be activated in <cell_type> infected monocytes </cell_type> through interaction of the cells with <protein> complement-opsonized particles </protein> and that enhanced viral replication is associated with <protein> C3 receptor </protein> -mediated nuclear translocation of the <protein> NF-kappa B complex </protein> ."
  },
  {
    "input_text": "Attenuation of gamma interferon -induced tyrosine phosphorylation in mononuclear phagocytes infected with Leishmania donovani : selective inhibition of signaling through Janus kinases and Stat1 .",
    "target_text": "Attenuation of <protein> gamma interferon </protein> -induced tyrosine phosphorylation in <cell_type> mononuclear phagocytes </cell_type> infected with Leishmania donovani : selective inhibition of signaling through <protein> Janus kinases </protein> and <protein> Stat1 </protein> ."
  },
  {
    "input_text": "The induction of gene transcription in response to gamma interferon is impaired in mononuclear phagocytes infected with Leishmania donovani , and the mechanisms involved are not fully understood .",
    "target_text": "The induction of gene transcription in response to <protein> gamma interferon </protein> is impaired in <cell_type> mononuclear phagocytes </cell_type> infected with Leishmania donovani , and the mechanisms involved are not fully understood ."
  },
  {
    "input_text": "The changes in gene expression brought about by gamma interferon are thought to involve transient increases in the activities of cellular protein tyrosine kinases , including the Janus kinases Jak1 and Jak2 , leading to tyrosine phosphorylation of the transcription factor Stat1 .",
    "target_text": "The changes in gene expression brought about by <protein> gamma interferon </protein> are thought to involve transient increases in the activities of <protein> cellular protein tyrosine kinases </protein> , including the <protein> Janus kinases </protein> <protein> Jak1 </protein> and <protein> Jak2 </protein> , leading to tyrosine phosphorylation of the <protein> transcription factor <protein> Stat1 </protein> </protein> ."
  },
  {
    "input_text": "To investigate the mechanisms accounting for the impaired responses to gamma interferon , a model system for examining overall changes in protein tyrosine phosphorylation , activation of Jak1 and Jak2 and phosphorylation of Stat1 was developed in phorbol 12-myristate 13-acetate -differentiated U-937 cells .",
    "target_text": "To investigate the mechanisms accounting for the impaired responses to <protein> gamma interferon </protein> , a model system for examining overall changes in protein tyrosine phosphorylation , activation of <protein> Jak1 </protein> and <protein> Jak2 </protein> and phosphorylation of <protein> Stat1 </protein> was developed in <cell_line> phorbol 12-myristate 13-acetate -differentiated U-937 cells </cell_line> ."
  },
  {
    "input_text": "Analysis of whole-cell lysates by antiphosphotyrosine immunoblotting showed that incubation with gamma interferon brought about specific increases in phosphotyrosine labeling of several proteins .",
    "target_text": "Analysis of whole-cell lysates by antiphosphotyrosine immunoblotting showed that incubation with <protein> gamma interferon </protein> brought about specific increases in phosphotyrosine labeling of several proteins ."
  },
  {
    "input_text": "Increased labeling of these proteins occurred to similar extents in control cells and in cells that had been infected with L. donovani for 16 h .",
    "target_text": "Increased labeling of these proteins occurred to similar extents in <cell_type> control cells </cell_type> and in cells that had been infected with L. donovani for 16 h ."
  },
  {
    "input_text": "Jak1 , Jak2 , and Stat1 were immunoprecipitated from control and interferon-treated cells , and tyrosine phosphorylation of these proteins , detected by antiphosphotyrosine immunoblotting was used to measured their activation .",
    "target_text": "<protein> Jak1 </protein> , <protein> Jak2 </protein> , and <protein> Stat1 </protein> were immunoprecipitated from control and <cell_line> interferon-treated cells </cell_line> , and tyrosine phosphorylation of these proteins , detected by antiphosphotyrosine immunoblotting was used to measured their activation ."
  },
  {
    "input_text": "Tyrosine phosphorylation of Jak1 , Jak2 , and Stat1 increased markedly , in a dose-dependent manner , in U-937 cells incubated with gamma interferon .",
    "target_text": "Tyrosine phosphorylation of <protein> Jak1 </protein> , <protein> Jak2 </protein> , and <protein> Stat1 </protein> increased markedly , in a dose-dependent manner , in <cell_line> U-937 cells </cell_line> incubated with <protein> gamma interferon </protein> ."
  },
  {
    "input_text": "In contrast , in cells infected with L. donovani , tyrosine phosphorylation of Jak1 , Jak2 , and Stat1 was markedly impaired .",
    "target_text": "In contrast , in cells infected with L. donovani , tyrosine phosphorylation of <protein> Jak1 </protein> , <protein> Jak2 </protein> , and <protein> Stat1 </protein> was markedly impaired ."
  },
  {
    "input_text": "This effect was dependent upon the duration of exposure to L. donovani and was maximal and complete at 16 h .",
    "target_text": "This effect was dependent upon the duration of exposure to L. donovani and was maximal and complete at 16 h ."
  },
  {
    "input_text": "Results similar to those observed with U-937 cells were also obtained with human peripheral blood monocytes .",
    "target_text": "Results similar to those observed with <cell_line> U-937 cells </cell_line> were also obtained with <cell_type> human peripheral blood monocytes </cell_type> ."
  },
  {
    "input_text": "These findings indicate that infection of human mononuclear phagocytes with L. donovani leads to impaired gamma interferon -mediated tyrosine phosphorylation and selective effects on the Jak- Stat1 pathway .",
    "target_text": "These findings indicate that infection of <cell_type> human mononuclear phagocytes </cell_type> with L. donovani leads to impaired <protein> gamma interferon </protein> -mediated tyrosine phosphorylation and selective effects on the Jak- <protein> Stat1 </protein> pathway ."
  },
  {
    "input_text": "Unresponsiveness to gamma interferon for activation of this pathway may explain impaired transcriptional responses in leishmania-infected cells .",
    "target_text": "Unresponsiveness to <protein> gamma interferon </protein> for activation of this pathway may explain impaired transcriptional responses in <cell_type> leishmania-infected cells </cell_type> ."
  },
  {
    "input_text": "Mutually exclusive interaction of a novel matrix attachment region binding protein and the NF-muNR enhancer repressor .",
    "target_text": "Mutually exclusive interaction of a novel <protein> matrix attachment region binding protein </protein> and the <protein> NF-muNR enhancer repressor </protein> ."
  },
  {
    "input_text": "Implications for regulation of immunoglobulin heavy chain expression .",
    "target_text": "Implications for regulation of <protein> immunoglobulin heavy chain </protein> expression ."
  },
  {
    "input_text": "The immunoglobulin heavy chain ( IgH ) intronic enhancer stimulates transcription from functional promoters in B lymphocytes but not other cell types .",
    "target_text": "The <protein> immunoglobulin heavy chain </protein> ( <protein> IgH </protein> ) intronic enhancer stimulates transcription from functional promoters in B lymphocytes but not other cell types ."
  },
  {
    "input_text": "The observation that binding sites for the nuclear factor-mu negative regulator ( NF-muNR ) enhancer repressor overlap nuclear matrix attachment regions ( MARs ) in this enhancer has lead to the hypothesis that the cell type specificity of the enhancer might be controlled by regulating nuclear matrix attachment ( Scheuermann , R. H. , and Chen , U. ( 1989 ) Genes & Dev. 3 , 1255-1266 ) .",
    "target_text": "The observation that binding sites for the <protein> <protein> nuclear factor-mu negative regulator </protein> ( <protein> NF-muNR </protein> ) enhancer repressor overlap <protein> nuclear matrix attachment regions </protein> </protein> ( <protein> MARs </protein> ) in this <DNA> enhancer </DNA> has lead to the hypothesis that the cell type specificity of the <DNA> enhancer </DNA> might be controlled by regulating nuclear matrix attachment ( Scheuermann , R. H. , and Chen , U. ( 1989 ) Genes & Dev. 3 , 1255-1266 ) ."
  },
  {
    "input_text": "To understand the role of MARs in IgH enhancer regulation , we have identified a novel MAR-binding protein , MAR-BP1 , from soluble nuclear matrix preparations based on its ability to bind to the MARs associated with the IgH enhancer .",
    "target_text": "To understand the role of <protein> MARs </protein> in <DNA> <protein> IgH </protein> enhancer </DNA> regulation , we have identified a novel <protein> MAR-binding protein </protein> , <protein> MAR-BP1 </protein> , from soluble nuclear matrix preparations based on its ability to bind to the <protein> MARs </protein> associated with the <DNA> <protein> IgH </protein> enhancer </DNA> ."
  },
  {
    "input_text": "Purified MAR-BP1 migrates as a 33-kDa protein , and it can be found in nuclear matrix preparations from a number of different types of lymphoid cell lines .",
    "target_text": "Purified <protein> MAR-BP1 </protein> migrates as a <protein> 33-kDa protein </protein> , and it can be found in nuclear matrix preparations from a number of different types of <cell_line> lymphoid cell lines </cell_line> ."
  },
  {
    "input_text": "Although specific binding sites have been difficult to localize by chemical or enzymatic footprinting procedures , NF-muNR binding sites are critical for efficient MAR-BP1 binding .",
    "target_text": "Although specific binding sites have been difficult to localize by chemical or enzymatic footprinting procedures , <protein> NF-muNR </protein> binding sites are critical for efficient <protein> MAR-BP1 </protein> binding ."
  },
  {
    "input_text": "Indeed , binding of the IgH enhancer to either intact nuclear matrix preparations or to MAR-BP1 is mutually exclusive to NF-muNR binding .",
    "target_text": "Indeed , binding of the <DNA> <protein> IgH </protein> enhancer </DNA> to either intact nuclear matrix preparations or to <protein> MAR-BP1 </protein> is mutually exclusive to <protein> NF-muNR </protein> binding ."
  },
  {
    "input_text": "These results are consistent with a model for cell-type specific regulation in which binding of the NF-muNR repressor to the IgH enhancer prevents nuclear matrix attachment in inappropriate cells by interfering with MAR-BP1 /enhancer interaction .",
    "target_text": "These results are consistent with a model for cell-type specific regulation in which binding of the <protein> <protein> NF-muNR </protein> repressor </protein> to the <DNA> <protein> IgH </protein> enhancer </DNA> prevents nuclear matrix attachment in inappropriate cells by interfering with <protein> MAR-BP1 </protein> <DNA> /enhancer </DNA> interaction ."
  },
  {
    "input_text": "PU.1 ( Spi-1 ) and C/EBP alpha regulate expression of the granulocyte-macrophage colony-stimulating factor receptor alpha gene .",
    "target_text": "<protein> PU.1 </protein> ( <protein> Spi-1 </protein> ) and <protein> C/EBP alpha </protein> regulate expression of the <DNA> <protein> granulocyte-macrophage colony-stimulating factor receptor </protein> alpha gene </DNA> ."
  },
  {
    "input_text": "Growth factor receptors play an important role in hematopoiesis .",
    "target_text": "<protein> Growth factor receptors </protein> play an important role in hematopoiesis ."
  },
  {
    "input_text": "In order to further understand the mechanisms directing the expression of these key regulators of hematopoiesis , we initiated a study investigating the transcription factors activating the expression of the granulocyte-macrophage colony-stimulating factor ( GM-CSF ) receptor alpha gene .",
    "target_text": "In order to further understand the mechanisms directing the expression of these key regulators of hematopoiesis , we initiated a study investigating the <protein> transcription factors </protein> activating the expression of the <DNA> <protein> granulocyte-macrophage colony-stimulating factor </protein> ( <protein> GM-CSF </protein> ) receptor alpha gene </DNA> ."
  },
  {
    "input_text": "Here , we demonstrate that the human GM-CSF receptor alpha promoter directs reporter gene activity in a tissue-specific fashion in myelomonocytic cells , which correlates with its expression pattern as analyzed by reverse transcription PCR .",
    "target_text": "Here , we demonstrate that the <DNA> human <protein> <protein> GM-CSF </protein> receptor alpha </protein> promoter </DNA> directs <DNA> reporter gene </DNA> activity in a tissue-specific fashion in <cell_type> myelomonocytic cells </cell_type> , which correlates with its expression pattern as analyzed by reverse transcription PCR ."
  },
  {
    "input_text": "The GM-CSF receptor alpha promoter contains an important functional site between positions -53 and -41 as identified by deletion analysis of reporter constructs .",
    "target_text": "The <DNA> <protein> <protein> GM-CSF </protein> receptor alpha </protein> promoter </DNA> contains an important functional site between positions -53 and -41 as identified by deletion analysis of <DNA> reporter constructs </DNA> ."
  },
  {
    "input_text": "We show that the myeloid and B cell transcription factor PU.1 binds specifically to this site .",
    "target_text": "We show that the myeloid and <protein> B cell transcription factor </protein> <protein> PU.1 </protein> binds specifically to this site ."
  },
  {
    "input_text": "Furthermore , we demonstrate that a CCAAT site located upstream of the PU.1 site between positions -70 and -54 is involved in positive-negative regulation of the GM-CSF receptor alpha promoter activity .",
    "target_text": "Furthermore , we demonstrate that a <DNA> CCAAT site </DNA> located upstream of the <DNA> <protein> PU.1 </protein> site </DNA> between positions -70 and -54 is involved in positive-negative regulation of the <DNA> <protein> <protein> GM-CSF </protein> receptor alpha </protein> promoter </DNA> activity ."
  },
  {
    "input_text": "C/EBP alpha is the major CCAAT/enhancer -binding protein ( C/EBP ) form binding to this site in nuclear extracts of U937 cells .",
    "target_text": "<protein> C/EBP alpha </protein> is the major <protein> <DNA> CCAAT/enhancer </DNA> -binding protein </protein> ( <protein> C/EBP </protein> ) form binding to this site in nuclear extracts of <cell_line> U937 cells </cell_line> ."
  },
  {
    "input_text": "Point mutations of either the PU.1 site or the C/EBP site that abolish the binding of the respective factors result in a significant decrease of GM-CSF receptor alpha promoter activity in myelomonocytic cells only .",
    "target_text": "Point mutations of either the <DNA> <protein> PU.1 </protein> site </DNA> or the <DNA> <protein> C/EBP </protein> site </DNA> that abolish the binding of the respective factors result in a significant decrease of <DNA> <protein> <protein> GM-CSF </protein> receptor alpha </protein> promoter </DNA> activity in <cell_type> myelomonocytic cells </cell_type> only ."
  },
  {
    "input_text": "Furthermore , we demonstrate that in myeloid and B cell extracts , PU.1 forms a novel , specific , more slowly migrating complex ( PU-SF ) when binding the GM-CSF receptor alpha promoter PU.1 site .",
    "target_text": "Furthermore , we demonstrate that in myeloid and B cell extracts , <protein> PU.1 </protein> forms a novel , specific , more slowly migrating complex ( <protein> PU-SF </protein> ) when binding the <DNA> <protein> <protein> GM-CSF </protein> receptor alpha </protein> promoter </DNA> <DNA> <protein> PU.1 </protein> site </DNA> ."
  },
  {
    "input_text": "This is the first demonstration of a specific interaction with PU.1 on a myeloid PU.1 binding site .",
    "target_text": "This is the first demonstration of a specific interaction with <protein> PU.1 </protein> on a <DNA> myeloid <protein> PU.1 </protein> binding site </DNA> ."
  },
  {
    "input_text": "The novel complex is distinct from that described previously as binding to B cell enhancer sites and can be formed by addition of PU.1 to extracts from certain nonmyeloid cell types which do not express PU.1 , including T cells and epithelial cells , but not from erythroid cells .",
    "target_text": "The novel complex is distinct from that described previously as binding to <DNA> B cell enhancer sites </DNA> and can be formed by addition of <protein> PU.1 </protein> to extracts from certain <cell_type> nonmyeloid cell types </cell_type> which do not express <protein> PU.1 </protein> , including <cell_type> T cells </cell_type> and <cell_type> epithelial cells </cell_type> , but not from <cell_type> erythroid cells </cell_type> ."
  },
  {
    "input_text": "Furthermore , we demonstrate that the PU-SF complex binds to PU.1 sites found on a number of myeloid promoters , and its formation requires an intact PU.1 site adjacent to a single-stranded region .",
    "target_text": "Furthermore , we demonstrate that the <protein> <protein> PU-SF </protein> complex </protein> binds to <protein> PU.1 </protein> sites found on a number of <DNA> myeloid promoters </DNA> , and its formation requires an intact <DNA> <protein> PU.1 </protein> site </DNA> adjacent to a single-stranded region ."
  },
  {
    "input_text": "Expression of PU.1 in nonmyeloid cells can activate the GM-CSF receptor alpha promoter .",
    "target_text": "Expression of <protein> PU.1 </protein> in <cell_type> nonmyeloid cells </cell_type> can activate the <DNA> <protein> GM-CSF </protein> receptor alpha promoter </DNA> ."
  },
  {
    "input_text": "Deletion of the amino-terminal region of PU.1 results in a failure to form the PU-SF complex and in a concomitant loss of transactivation , suggesting that formation of the PU-SF complex is of functional importance for the activity of the GM-CSF receptor alpha promoter .",
    "target_text": "Deletion of the <protein> amino-terminal region </protein> of <protein> PU.1 </protein> results in a failure to form the <protein> PU-SF </protein> complex and in a concomitant loss of transactivation , suggesting that formation of the <protein> <protein> PU-SF </protein> complex </protein> is of functional importance for the activity of the <DNA> <protein> GM-CSF </protein> receptor alpha promoter </DNA> ."
  },
  {
    "input_text": "Finally , we demonstrate that C/EBP alpha can also active the GM-CSF receptor alpha promoter in nonmyeloid cells .",
    "target_text": "Finally , we demonstrate that <protein> <protein> C/EBP </protein> alpha </protein> can also active the <DNA> <protein> <protein> GM-CSF </protein> receptor alpha </protein> promoter </DNA> in <cell_type> nonmyeloid cells </cell_type> ."
  },
  {
    "input_text": "( ABSTRACT TRUNCATED AT 400 WORDS )",
    "target_text": "( ABSTRACT TRUNCATED AT 400 WORDS )"
  },
  {
    "input_text": "HMG-I binds to GATA motifs : implications for an HPFH syndrome .",
    "target_text": "<protein> HMG-I </protein> binds to <DNA> GATA motifs </DNA> : implications for an HPFH syndrome ."
  },
  {
    "input_text": "We have examined binding of the nuclear protein HMG-I to the human gamma-globin promoter .",
    "target_text": "We have examined binding of the <protein> nuclear protein </protein> <protein> HMG-I </protein> to the <DNA> human gamma-globin promoter </DNA> ."
  },
  {
    "input_text": "We find that HMG-I binds preferentially to the more 3' of a pair of GATA motifs in the gamma-globin promoter ; this paired motif is bound by the erythroid factor GATA-1 .",
    "target_text": "We find that <protein> HMG-I </protein> binds preferentially to the more 3' of a pair of <DNA> GATA motifs </DNA> in the <DNA> gamma-globin promoter </DNA> ; this paired motif is bound by the <protein> erythroid factor <protein> GATA-1 </protein> </protein> ."
  },
  {
    "input_text": "A naturally occurring mutation ( -175 T-C ) in the area bound by HMG-I results in overexpression of gamma-globin in adult red blood cells ( HPFH ) and up-regulation of the gamma-globin promoter in in vitro expression assays ; HMG-I does not bind to this mutant sequence .",
    "target_text": "A naturally occurring mutation ( -175 T-C ) in the area bound by <protein> HMG-I </protein> results in overexpression of <protein> gamma-globin </protein> in <cell_type> adult red blood cells </cell_type> ( <cell_type> HPFH </cell_type> ) and up-regulation of the <DNA> <protein> gamma-globin </protein> promoter </DNA> in in vitro expression assays ; <protein> HMG-I </protein> does not bind to this <DNA> mutant sequence </DNA> ."
  },
  {
    "input_text": "A survey of GATA motifs from other globin cis-elements demonstrates HMG-I binding to most of them .",
    "target_text": "A survey of <DNA> GATA motifs </DNA> from other <DNA> globin cis-elements </DNA> demonstrates <protein> HMG-I </protein> binding to most of them ."
  },
  {
    "input_text": "These findings implicate HMG-I in the HPFH phenotype ; we speculate that it may participate in the formation of multiprotein complexes that regulate globin gene expression .",
    "target_text": "These findings implicate <protein> HMG-I </protein> in the <cell_type> HPFH </cell_type> phenotype ; we speculate that it may participate in the formation of <protein> multiprotein complexes </protein> that regulate globin gene expression ."
  },
  {
    "input_text": "Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 ( HTLV-1 ) tax protein or virus-transformed cells .",
    "target_text": "Constitutive activation of different <protein> Jak tyrosine kinases </protein> in <protein> human T cell leukemia virus type 1 ( HTLV-1 ) tax protein </protein> or <cell_line> virus-transformed cells </cell_line> ."
  },
  {
    "input_text": "HTLV-1 infection causes an adult T cell leukemia in humans .",
    "target_text": "HTLV-1 infection causes an adult T cell leukemia in humans ."
  },
  {
    "input_text": "The viral encoded protein tax , is thought to play an important role in oncogenesis .",
    "target_text": "The <protein> viral encoded protein </protein> <protein> tax </protein> , is thought to play an important role in oncogenesis ."
  },
  {
    "input_text": "Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes , despite comparable levels of tax expression in both tissues .",
    "target_text": "Our previous data obtained from a <protein> tax </protein> transgenic mouse model revealed that <protein> tax </protein> transforms <cell_type> mouse fibroblasts </cell_type> but not <cell_type> thymocytes </cell_type> , despite comparable levels of <protein> tax </protein> expression in both tissues ."
  },
  {
    "input_text": "Constitutive tyrosine phosphorylation of a 130-kD protein ( s ) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines , but not in thymocytes from Thy-tax transgenic mice .",
    "target_text": "Constitutive tyrosine phosphorylation of a <protein> 130-kD protein </protein> ( s ) was observed in the <protein> tax </protein> <cell_line> transformed fibroblast B line </cell_line> and in <cell_line> HTLV-1 transformed human lymphoid lines </cell_line> , but not in <cell_type> thymocytes </cell_type> from Thy-tax transgenic mice ."
  },
  {
    "input_text": "Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies , identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines .",
    "target_text": "Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of <protein> <protein> Jak kinase </protein> specific antibodies </protein> , identified p130 as <protein> Jak2 </protein> in the <protein> tax </protein> transformed <cell_line> mouse fibroblastic cell line </cell_line> and <protein> Jak3 </protein> in <cell_line> HTLV-1 transformed human T cell lines </cell_line> ."
  },
  {
    "input_text": "Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6 .",
    "target_text": "Phosphorylation of <protein> Jak2 </protein> in <cell_line> <protein> tax </protein> transformed cells </cell_line> resulted from high expression of <protein> IL-6 </protein> ."
  },
  {
    "input_text": "Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line , which was associated with induction of cell proliferation .",
    "target_text": "Tyrosine phosphorylation of this protein could also be induced in <cell_line> Balb/c3T3 cells </cell_line> using a supernatant from the <cell_line> B line </cell_line> , which was associated with induction of cell proliferation ."
  },
  {
    "input_text": "Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies .",
    "target_text": "Both phosphorylation and proliferation were inhibited by <protein> <protein> IL-6 </protein> neutralizing antibodies </protein> ."
  },
  {
    "input_text": "Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model .",
    "target_text": "Constitutive phosphorylation of <protein> Jak kinases </protein> may facilitate tumor growth in both <cell_type> HTLV-1 infected human <cell_type> T cells </cell_type> </cell_type> and the transgenic mouse model ."
  },
  {
    "input_text": "Regulation of c-jun mRNA expression by hydroxyurea in human K562 cells during erythroid differentiation [ published erratum appears in Biochim Biophys Acta 1995 Dec 27 ; 1264 ( 3 ) : 409 ]",
    "target_text": "Regulation of <RNA> <DNA> c-jun </DNA> mRNA </RNA> expression by hydroxyurea in <cell_line> human K562 cells </cell_line> during erythroid differentiation [ published erratum appears in Biochim Biophys Acta 1995 Dec 27 ; 1264 ( 3 ) : 409 ]"
  },
  {
    "input_text": "Hydroxyurea ( HU ) is an antitumor agent which also induces hemoglobinization during erythroid differentiation .",
    "target_text": "Hydroxyurea ( HU ) is an antitumor agent which also induces hemoglobinization during erythroid differentiation ."
  },
  {
    "input_text": "In addition , HU stimulates the synthesis of fetal hemoglobin in sickle cell anemia patients .",
    "target_text": "In addition , HU stimulates the synthesis of <protein> fetal hemoglobin </protein> in sickle cell anemia patients ."
  },
  {
    "input_text": "To further understand its mechanism of action , we investigated the effects of HU on regulation of c-jun expression prior to the onset of erythroid differentiation of K562 cells .",
    "target_text": "To further understand its mechanism of action , we investigated the effects of HU on regulation of <DNA> c-jun </DNA> expression prior to the onset of erythroid differentiation of <cell_line> K562 cells </cell_line> ."
  },
  {
    "input_text": "HU induced a dose-dependent stimulation of c-jun synthesis .",
    "target_text": "HU induced a dose-dependent stimulation of <DNA> c-jun </DNA> synthesis ."
  },
  {
    "input_text": "The levels of c-jun mRNA was elevated 4 to 7.5-fold by HU within 2 h .",
    "target_text": "The levels of <RNA> <DNA> c-jun </DNA> mRNA </RNA> was elevated 4 to 7.5-fold by HU within 2 h ."
  },
  {
    "input_text": "This was followed by a gradual decline to the basal level by 24 h .",
    "target_text": "This was followed by a gradual decline to the basal level by 24 h ."
  },
  {
    "input_text": "Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates c-jun mRNA expression by increasing the rate of synthesis as well as stabilizing the c-jun mRNA .",
    "target_text": "Both nuclear run-on and actinomycin D pulse experiments strongly indicate that HU regulates <RNA> c-jun mRNA </RNA> expression by increasing the rate of synthesis as well as stabilizing the <RNA> <DNA> c-jun </DNA> mRNA </RNA> ."
  },
  {
    "input_text": "In addition , the level of jun protein was elevated by 2 to 5-fold within 4 h in HU treated cells .",
    "target_text": "In addition , the level of <protein> jun protein </protein> was elevated by 2 to 5-fold within 4 h in <cell_line> HU treated cells </cell_line> ."
  },
  {
    "input_text": "Furthermore , concentrations of HU below 250 microM slightly increased the 5X AP-1 /CAT activity .",
    "target_text": "Furthermore , concentrations of HU below 250 microM slightly increased the 5X <protein> AP-1 </protein> <protein> /CAT </protein> activity ."
  },
  {
    "input_text": "These results strongly suggest that HU induces both transcriptional and post-transcription regulation of c-jun during erythroid differentiation .",
    "target_text": "These results strongly suggest that HU induces both transcriptional and post-transcription regulation of <DNA> c-jun </DNA> during erythroid differentiation ."
  },
  {
    "input_text": "In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in man : relationship to glucocorticoid receptors .",
    "target_text": "In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in man : relationship to <protein> glucocorticoid receptors </protein> ."
  },
  {
    "input_text": "Interrelations between the hypothalamic-pituitary-adrenal system ( HPA ) and the immune system represent a well-documented biological phenomenon .",
    "target_text": "Interrelations between the hypothalamic-pituitary-adrenal system ( HPA ) and the immune system represent a well-documented biological phenomenon ."
  },
  {
    "input_text": "While in vitro administration of glucocorticoids may inhibit concanavalin A ( Con A ) - and phytohemagglutinin ( PHA ) - induced T-cell proliferation , pokeweed mitogen ( PWM ) -driven B-cell mitogenesis is relatively resistant to glucocorticoids .",
    "target_text": "While in vitro administration of glucocorticoids may inhibit concanavalin A ( Con A ) - and phytohemagglutinin ( PHA ) - induced T-cell proliferation , <protein> pokeweed mitogen </protein> ( <protein> PWM </protein> ) -driven B-cell mitogenesis is relatively resistant to glucocorticoids ."
  },
  {
    "input_text": "To further explore the link between the HPA and the immune system in relation to glucocorticoid receptor function , dose-response curves were obtained for Con A - and PHA -induced T-cell mitogenesis , PWM -generated B-cell mitogenesis and spontaneous lymphocyte proliferation in 13 healthy controls .",
    "target_text": "To further explore the link between the HPA and the immune system in relation to <protein> glucocorticoid receptor </protein> function , dose-response curves were obtained for Con A - and <protein> PHA </protein> -induced T-cell mitogenesis , <protein> PWM </protein> -generated B-cell mitogenesis and spontaneous lymphocyte proliferation in 13 healthy controls ."
  },
  {
    "input_text": "Glucocorticoid effects were assessed in vivo by depletion of endogenous glucocorticoids after oral administration of 1.5 g metyrapone ( MET ) and subsequent glucocorticoid replacement , and in vitro by incubation of the cells with different doses of dexamethasone ( DEX ) .",
    "target_text": "Glucocorticoid effects were assessed in vivo by depletion of endogenous glucocorticoids after oral administration of 1.5 g metyrapone ( MET ) and subsequent glucocorticoid replacement , and in vitro by incubation of the cells with different doses of dexamethasone ( DEX ) ."
  },
  {
    "input_text": "There was a significant decrease in PWM -induced B-cell mitogenesis and a more pronounced effect of DEX administered in vitro on spontaneous lymphocyte proliferation after MET treatment when compared with the DEX plus MET pretreated condition in vivo .",
    "target_text": "There was a significant decrease in <protein> PWM </protein> -induced B-cell mitogenesis and a more pronounced effect of DEX administered in vitro on spontaneous lymphocyte proliferation after MET treatment when compared with the DEX plus MET pretreated condition in vivo ."
  },
  {
    "input_text": "These data suggest that the inhibition of spontaneous lymphocyte proliferation by glucocorticoids in vitro is related to glucocorticoid receptor function .",
    "target_text": "These data suggest that the inhibition of spontaneous lymphocyte proliferation by glucocorticoids in vitro is related to <protein> glucocorticoid receptor </protein> function ."
  },
  {
    "input_text": "The decrease in PWM -generated B-cell proliferation following cortisol depletion by MET may be seen in connection with impaired glucocorticoid -mediated induction of interleukin-1 receptor synthesis .",
    "target_text": "The decrease in <protein> PWM </protein> -generated B-cell proliferation following cortisol depletion by MET may be seen in connection with impaired glucocorticoid -mediated induction of <protein> interleukin-1 receptor </protein> synthesis ."
  },
  {
    "input_text": "Transcription specific differences visualized by fluorescence in situ hybridization pattern on interphase nuclei of different cell types .",
    "target_text": "Transcription specific differences visualized by fluorescence in situ hybridization pattern on interphase nuclei of different cell types ."
  },
  {
    "input_text": "Application of a \" formamide free \" and thus \" material preserving \" in situ hybridization technique using the cDNA of the myf3 gene revealed the following results : Human rhabdomyosarcoma cells , characterized by a high expression of myf3 show intensive hybridization signals in their interphase .",
    "target_text": "Application of a \" formamide free \" and thus \" material preserving \" in situ hybridization technique using the <DNA> cDNA </DNA> of the <DNA> myf3 gene </DNA> revealed the following results : <cell_type> Human rhabdomyosarcoma cells </cell_type> , characterized by a high expression of <DNA> myf3 </DNA> show intensive hybridization signals in their interphase ."
  },
  {
    "input_text": "RNase treatment prior to hybridization considerably reduces the size of this signals .",
    "target_text": "<protein> RNase </protein> treatment prior to hybridization considerably reduces the size of this signals ."
  },
  {
    "input_text": "In comparison , isolated nuclei of human lymphocytes in which no need for the expression of this gene exists , show barely hybridization signals .",
    "target_text": "In comparison , isolated nuclei of <cell_type> human lymphocytes </cell_type> in which no need for the expression of this gene exists , show barely hybridization signals ."
  },
  {
    "input_text": "Correspondingly , RNase treatment had no effect on hybridization pattern at all .",
    "target_text": "Correspondingly , <protein> RNase </protein> treatment had no effect on hybridization pattern at all ."
  },
  {
    "input_text": "In conclusion an increased transcription efficiency of a cell type specific gene is accompanied by a higher hybridization accessibility in the corresponding cell nuclei .",
    "target_text": "In conclusion an increased transcription efficiency of a cell type specific gene is accompanied by a higher hybridization accessibility in the corresponding cell nuclei ."
  },
  {
    "input_text": "Oncogenicity of human papillomavirus- or adenovirus- transformed cells correlates with resistance to lysis by natural killer cells .",
    "target_text": "Oncogenicity of human papillomavirus- or adenovirus- transformed cells correlates with resistance to lysis by <cell_type> natural killer cells </cell_type> ."
  },
  {
    "input_text": "The reasons for the dissimilar oncogenicities of human adenoviruses and human papillomaviruses ( HPV ) in humans are unknown but may relate to differences in the capacities of the E1A and E7 proteins to target cells for rejection by the host natural killer ( NK ) cell response .",
    "target_text": "The reasons for the dissimilar oncogenicities of human adenoviruses and human papillomaviruses ( HPV ) in humans are unknown but may relate to differences in the capacities of the <protein> E1A </protein> and <protein> E7 proteins </protein> to <cell_type> target cells </cell_type> for rejection by the <cell_type> host natural killer ( NK ) cell </cell_type> response ."
  },
  {
    "input_text": "As one test of this hypothesis , we compared the abilities of E1A - and E7 -expressing human fibroblastic or keratinocyte-derived human cells to be selectively killed by either unstimulated or interferon ( IFN ) -activated NK cells .",
    "target_text": "As one test of this hypothesis , we compared the abilities of <protein> E1A </protein> - and <protein> E7 </protein> -expressing human fibroblastic or keratinocyte-derived human cells to be selectively killed by either <cell_type> unstimulated </cell_type> or <cell_line> interferon ( IFN ) -activated NK cells </cell_line> ."
  },
  {
    "input_text": "Cells expressing the E1A oncoprotein were selectively killed by unstimulated NK cells , while the same parental cells but expressing the HPV type 16 ( HPV-16 ) or HPV-18 E7 oncoprotein were resistant to NK cell lysis .",
    "target_text": "Cells expressing the <protein> <protein> E1A </protein> oncoprotein </protein> were selectively killed by <cell_line> unstimulated NK cells </cell_line> , while the same <cell_type> parental cells </cell_type> but expressing the HPV type 16 ( HPV-16 ) or HPV-18 <protein> <protein> E7 </protein> oncoprotein </protein> were resistant to NK cell lysis ."
  },
  {
    "input_text": "The ability of IFN-activated NK cells to selectively kill virally transformed cells depends on IFN 's ability to induce resistance to NK cell lysis in normal ( i.e. , non-viral oncogene-expressing ) but not virally transformed cells .",
    "target_text": "The ability of <cell_line> IFN-activated NK cells </cell_line> to selectively kill virally transformed cells depends on <protein> IFN </protein> 's ability to induce resistance to NK cell lysis in normal ( i.e. , <cell_line> non-viral oncogene-expressing </cell_line> ) but not <cell_line> virally transformed cells </cell_line> ."
  },
  {
    "input_text": "E1A blocked IFN 's induction of cytolytic resistance , resulting in the selective lysis of adenovirus-transformed cells by IFN -activated NK cells .",
    "target_text": "<protein> E1A </protein> blocked <protein> IFN </protein> 's induction of cytolytic resistance , resulting in the selective lysis of <cell_line> adenovirus-transformed cells </cell_line> by <cell_line> <protein> IFN </protein> -activated NK cells </cell_line> ."
  },
  {
    "input_text": "The extent of IFN -induced NK cell killing of E1A -expressing cells was proportional to the level of E1A expression and correlated with the ability of E1A to block IFN -stimulated gene expression in target cells .",
    "target_text": "The extent of <protein> IFN </protein> -induced NK cell killing of <cell_line> <protein> E1A </protein> -expressing cells </cell_line> was proportional to the level of <protein> E1A </protein> expression and correlated with the ability of <protein> E1A </protein> to block <protein> IFN </protein> -stimulated gene expression in <cell_type> target cells </cell_type> ."
  },
  {
    "input_text": "In contrast , E7 blocked neither IFN -stimulated gene expression nor IFN 's induction of cytolytic resistance , thereby precluding the selective lysis of HPV -transformed cells by IFN -activated NK cells .",
    "target_text": "In contrast , <protein> E7 </protein> blocked neither <protein> IFN </protein> -stimulated gene expression nor <protein> IFN </protein> 's induction of cytolytic resistance , thereby precluding the selective lysis of <cell_line> HPV -transformed cells </cell_line> by <cell_line> <protein> IFN </protein> -activated NK cells </cell_line> ."
  },
  {
    "input_text": "In conclusion , E1A expression marks cells for destruction by the host NK cell response , whereas the E7 oncoprotein lacks this activity .",
    "target_text": "In conclusion , <protein> E1A </protein> expression marks cells for destruction by the host <cell_type> NK cell </cell_type> response , whereas the <protein> <protein> E7 </protein> oncoprotein </protein> lacks this activity ."
  },
  {
    "input_text": "Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)- dependent signal transduction pathways .",
    "target_text": "Regulation of <protein> IkB alpha </protein> phosphorylation by PKC- and Ca(2+)- dependent signal transduction pathways ."
  },
  {
    "input_text": "The Ca(2+) -dependent phosphatase calcineurin , a target of FK506 and CsA , synergizes with PKC -induced activation of nuclear factor ( NF ) -kappa B in T cell lines .",
    "target_text": "The <protein> Ca(2+) -dependent phosphatase </protein> <protein> calcineurin </protein> , a target of FK506 and CsA , synergizes with <protein> PKC </protein> -induced activation of <protein> nuclear factor ( NF ) -kappa B </protein> in <cell_line> T cell lines </cell_line> ."
  },
  {
    "input_text": "We have investigated whether this synergy is present in other cell types and the mechanism ( s ) by which these two pathways lead to NF-kappa B activation .",
    "target_text": "We have investigated whether this synergy is present in other cell types and the mechanism ( s ) by which these two pathways lead to <protein> NF-kappa B </protein> activation ."
  },
  {
    "input_text": "While this synergy is present in other cell types , in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B .",
    "target_text": "While this synergy is present in other cell types , in the <cell_line> monocytic cell line U937 </cell_line> <protein> calcineurin </protein> is also sufficient to activate <protein> NF-kappa B </protein> ."
  },
  {
    "input_text": "Having previously shown that Ca(2+)- and PKC- dependent pathways synergize by accelerating the degradation of IkB alpha , we focused on the regulation of IkB alpha phosphorylation .",
    "target_text": "Having previously shown that Ca(2+)- and PKC- dependent pathways synergize by accelerating the degradation of <protein> IkB alpha </protein> , we focused on the regulation of <protein> IkB alpha </protein> phosphorylation ."
  },
  {
    "input_text": "While PKC -dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines , co-activation of Ca(2+) -dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation .",
    "target_text": "While <protein> PKC </protein> -dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of <protein> IkB alpha </protein> in <cell_line> T cell lines </cell_line> , co-activation of Ca(2+) -dependent pathways accelerates the rate of <protein> IkB alpha </protein> phosphorylation and results in its complete degradation ."
  },
  {
    "input_text": "Activation of Ca(2+) -dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells .",
    "target_text": "Activation of Ca(2+) -dependent pathways alone do not result in the phosphorylation and/or degradation of <protein> IkB alpha </protein> in <cell_line> Jurkat T </cell_line> or in <cell_line> U937 cells </cell_line> ."
  },
  {
    "input_text": "Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA -induced IkB alpha phosphorylation /degradation irrespective of activation of Ca(2+) -dependent pathways , but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha , a PKC -independent stimulus .",
    "target_text": "Treatment of <cell_type> T cells </cell_type> with the selective <protein> PKC </protein> inhibitor GF109203X abrogates the PMA -induced <protein> IkB alpha </protein> phosphorylation /degradation irrespective of activation of Ca(2+) -dependent pathways , but not the phosphorylation and degradation of <protein> IkB alpha </protein> induced by <protein> TNF-alpha </protein> , a <protein> PKC </protein> -independent stimulus ."
  },
  {
    "input_text": "Contrary to the interaction with PKC , Ca(2+) -dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation , but at the level of its degradation .",
    "target_text": "Contrary to the interaction with <protein> PKC </protein> , Ca(2+) -dependent pathways synergize with <protein> TNF-alpha </protein> not at the level of <protein> IkB alpha </protein> phosphorylation , but at the level of its degradation ."
  },
  {
    "input_text": "These results indicate that Ca(2+) -dependent pathways , including the phosphatase calcineurin , participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC -dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation .",
    "target_text": "These results indicate that Ca(2+) -dependent pathways , including the <protein> phosphatase </protein> <protein> calcineurin </protein> , participate in the regulation of <protein> NF-kappa B </protein> in a cell specific fashion and synergize with <protein> PKC </protein> -dependent and -independent pathways at the level of <protein> IkB alpha </protein> phosphorylation and degradation ."
  },
  {
    "input_text": "Vitamin E therapy of acute CCl4 -induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding .",
    "target_text": "Vitamin E therapy of acute CCl4 -induced hepatic injury in mice is associated with inhibition of <protein> nuclear factor kappa B </protein> binding ."
  },
  {
    "input_text": "Oxidative stress , with reactive oxygen intermediate formation , may represent a common mechanism by which liver injury is induced by diverse etiologies .",
    "target_text": "Oxidative stress , with reactive oxygen intermediate formation , may represent a common mechanism by which liver injury is induced by diverse etiologies ."
  },
  {
    "input_text": "Oxidative stress enhances nuclear factor kappa B ( NF-kappa B ) activity , and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines .",
    "target_text": "Oxidative stress enhances <protein> nuclear factor kappa B </protein> ( <protein> NF-kappa B </protein> ) activity , and <protein> NF-kappa B </protein> activity has been shown to enhance the expression of <protein> cytotoxic cytokines </protein> ."
  },
  {
    "input_text": "Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice .",
    "target_text": "Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice ."
  },
  {
    "input_text": "This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol .",
    "target_text": "This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol ."
  },
  {
    "input_text": "Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice .",
    "target_text": "Alpha-tocopherol treatment of the mice given the CCl4 also reduced the <protein> NF-kappa B </protein> binding to levels approaching those found in normal mice ."
  },
  {
    "input_text": "In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha ( TNF-alpha ) messenger RNA levels .",
    "target_text": "In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced <protein> NF-kappa B </protein> binding and an increase in <RNA> <protein> tumor necrosis factor-alpha </protein> ( <protein> TNF-alpha </protein> ) messenger RNA </RNA> levels ."
  },
  {
    "input_text": "Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers .",
    "target_text": "Liver specimens taken from patients with acute fulminant hepatitis had markedly increased <protein> NF-kappa B </protein> binding activity in comparison with the binding of normal livers ."
  },
  {
    "input_text": "These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol , a free radical scavenger , also eliminated increased NF-kappa B binding .",
    "target_text": "These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol , a free radical scavenger , also eliminated increased <protein> NF-kappa B </protein> binding ."
  },
  {
    "input_text": "It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury , perhaps through an effect on cytotoxic cytokine synthesis .",
    "target_text": "It is tempting to speculate that enhanced <protein> NF-kappa B </protein> expression caused by free radical production/oxidative stress may modulate liver injury , perhaps through an effect on <protein> cytotoxic cytokine </protein> synthesis ."
  },
  {
    "input_text": "Immunosuppression by glucocorticoids : inhibition of NF-kappa B activity through induction of I kappa B synthesis [ see comments ]",
    "target_text": "Immunosuppression by glucocorticoids : inhibition of <protein> NF-kappa B </protein> activity through induction of <protein> I kappa B </protein> synthesis [ see comments ]"
  },
  {
    "input_text": "Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents .",
    "target_text": "Glucocorticoids are among the most potent anti-inflammatory and immunosuppressive agents ."
  },
  {
    "input_text": "They inhibit synthesis of almost all known cytokines and of several cell surface molecules required for immune function , but the mechanism underlying this activity has been unclear . Here it is shown that glucocorticoids are potent inhibitors of nuclear factor kappa B ( NF-kappa B ) activation in mice and cultured cells .",
    "target_text": "They inhibit synthesis of almost all known <protein> cytokines </protein> and of several <protein> cell surface molecules </protein> required for immune function , but the mechanism underlying this activity has been unclear . Here it is shown that glucocorticoids are potent inhibitors of <protein> nuclear factor kappa B </protein> ( <protein> NF-kappa B </protein> ) activation in mice and <cell_line> cultured cells </cell_line> ."
  },
  {
    "input_text": "This inhibition is mediated by induction of the I kappa B alpha inhibitory protein , which traps activated NF-kappa B in inactive cytoplasmic complexes .",
    "target_text": "This inhibition is mediated by induction of the <protein> I kappa B </protein> alpha inhibitory protein , which traps activated <protein> NF-kappa B </protein> in <protein> inactive cytoplasmic complexes </protein> ."
  },
  {
    "input_text": "Because NF-kappa B activates many immunoregulatory genes in response to pro-inflammatory stimuli , the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids .",
    "target_text": "Because <protein> NF-kappa B </protein> activates many <DNA> immunoregulatory genes </DNA> in response to pro-inflammatory stimuli , the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids ."
  },
  {
    "input_text": "Transcriptional repression of the interleukin-2 gene by vitamin D3 : direct inhibition of NFATp /AP-1 complex formation by a nuclear hormone receptor .",
    "target_text": "Transcriptional repression of the <DNA> interleukin-2 gene </DNA> by vitamin D3 : direct inhibition of <protein> NFATp /AP-1 complex </protein> formation by a <protein> nuclear hormone receptor </protein> ."
  },
  {
    "input_text": "T- lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [ 1,25(OH)2D3 ] , the active metabolite of vitamin D3 , and is associated with a decrease in interleukin 2 ( IL-2 ) , gamma interferon , and granulocyte-macrophage colony-stimulating factor mRNA levels .",
    "target_text": "T- lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [ 1,25(OH)2D3 ] , the active metabolite of vitamin D3 , and is associated with a decrease in interleukin 2 ( IL-2 ) , gamma interferon , and granulocyte-macrophage colony-stimulating factor mRNA levels ."
  },
  {
    "input_text": "We report here that 1,25(OH)2D3 -mediated repression in Jurkat cells is cycloheximide resistant , suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor ( VDR ) .",
    "target_text": "We report here that 1,25(OH)2D3 -mediated repression in <cell_line> Jurkat cells </cell_line> is cycloheximide resistant , suggesting that it is a direct transcriptional repressive effect on <protein> IL-2 </protein> expression by the <protein> vitamin D3 receptor </protein> ( <protein> VDR </protein> ) ."
  },
  {
    "input_text": "We therefore examined vitamin D3 -mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter /reporter constructs and a VDR overexpression vector and by DNA binding .",
    "target_text": "We therefore examined vitamin D3 -mediated repression of activated <protein> IL-2 </protein> expression by cotransfecting <cell_line> Jurkat cells </cell_line> with <DNA> <protein> IL-2 </protein> promoter /reporter constructs </DNA> and a <DNA> <protein> VDR </protein> overexpression vector </DNA> and by DNA binding ."
  },
  {
    "input_text": "We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3 -mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element , NF-AT-1 , which is bound by a T-cell-specific transcription factor , NFATp , as well as by AP-1 .",
    "target_text": "We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3 -mediated repression in vivo to a short <DNA> 40-bp region </DNA> encompassing an important <DNA> positive regulatory element </DNA> , <DNA> NF-AT-1 </DNA> , which is bound by a <protein> T-cell-specific transcription factor </protein> , <protein> NFATp </protein> , as well as by <protein> AP-1 </protein> ."
  },
  {
    "input_text": "VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo ; the VDR DNA-binding domain alone , however , bound the element but also could not repress IL-2 expression .",
    "target_text": "<protein> <protein> VDR </protein> DNA-binding mutants </protein> were unable to either bind to this element in vitro or repress in vivo ; the <protein> <protein> VDR </protein> DNA-binding domain </protein> alone , however , bound the element but also could not repress <protein> IL-2 </protein> expression ."
  },
  {
    "input_text": "These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression .",
    "target_text": "These results indicate that DNA binding by <protein> VDR </protein> is necessary but not sufficient to mediate <protein> IL-2 </protein> repression ."
  },
  {
    "input_text": "By combining partially purified proteins in vitro , we observed the loss of the bound NFATp /AP-1-DNA complex upon inclusion of VDR or VDR -retinoid X receptor .",
    "target_text": "By combining <protein> partially purified proteins </protein> in vitro , we observed the loss of the bound <protein> <protein> NFATp </protein> /AP-1-DNA complex </protein> upon inclusion of <protein> VDR </protein> or <protein> <protein> VDR </protein> -retinoid X receptor </protein> ."
  },
  {
    "input_text": "Order of addition and off-rate experiments indicate that the VDR -retinoid X receptor heterodimer blocks NFATp / AP-1 complex formation and then stably associates with the NF-AT-1 element .",
    "target_text": "Order of addition and off-rate experiments indicate that the <protein> <protein> VDR </protein> -retinoid X receptor heterodimer </protein> blocks <protein> <protein> NFATp </protein> / <protein> AP-1 </protein> complex </protein> formation and then stably associates with the <DNA> <DNA> NF-AT-1 </DNA> element </DNA> ."
  },
  {
    "input_text": "This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents .",
    "target_text": "This direct inhibition by a nuclear hormone receptor of <protein> transcriptional activators </protein> of the <DNA> <protein> IL-2 </protein> gene </DNA> may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents ."
  },
  {
    "input_text": "Tissue-specific regulation of the rabbit 15-lipoxygenase gene in erythroid cells by a transcriptional silencer .",
    "target_text": "Tissue-specific regulation of the <DNA> rabbit <protein> 15-lipoxygenase </protein> gene </DNA> in <cell_type> erythroid cells </cell_type> by a <DNA> transcriptional silencer </DNA> ."
  },
  {
    "input_text": "The 15-lipoxygenase ( lox ) gene is expressed in a tissue-specific manner , predominantly in erythroid cells but also in airway epithelial cells and eosinophils .",
    "target_text": "The <DNA> 15-lipoxygenase ( lox ) gene </DNA> is expressed in a tissue-specific manner , predominantly in <cell_type> erythroid cells </cell_type> but also in <cell_type> airway epithelial cells </cell_type> and <cell_type> eosinophils </cell_type> ."
  },
  {
    "input_text": "We demonstrate in this report that the 5' flanking DNA of the 15-lox gene contains sequences which down-regulate its activity in a variety of non-erythroid cell lines but not in two erythroid cell lines .",
    "target_text": "We demonstrate in this report that the <DNA> 5' flanking DNA </DNA> of the <DNA> 15-lox gene </DNA> contains sequences which down-regulate its activity in a variety of <cell_line> non-erythroid cell lines </cell_line> but not in two <cell_line> erythroid cell lines </cell_line> ."
  },
  {
    "input_text": "The element has characteristics of a transcriptional ' silencer ' since it functions in both orientations .",
    "target_text": "The element has characteristics of a <DNA> transcriptional ' silencer ' </DNA> since it functions in both orientations ."
  },
  {
    "input_text": "The main activity of the silencer has been mapped to the first 900 bp of 5' flanking DNA , which contains nine binding sites for a nuclear factor present in non- erythroid cells but not in erythroid cells .",
    "target_text": "The main activity of the <DNA> silencer </DNA> has been mapped to the first 900 bp of <DNA> 5' flanking DNA </DNA> , which contains nine binding sites for a <protein> nuclear factor </protein> present in non- <cell_type> erythroid cells </cell_type> but not in <cell_type> erythroid cells </cell_type> ."
  },
  {
    "input_text": "These binding sites have similar sequences and multiple copies of the binding sites confer tissue-specific down-regulation when attached to a minimal lox promoter fragment .",
    "target_text": "These binding sites have similar sequences and multiple copies of the <DNA> binding sites </DNA> confer tissue-specific down-regulation when attached to a <DNA> minimal <DNA> lox promoter </DNA> fragment </DNA> ."
  },
  {
    "input_text": "The 5' flanking DNA also contains a cluster of three binding sites for the GATA family of transcription factors .",
    "target_text": "The <DNA> 5' flanking DNA </DNA> also contains a cluster of three <DNA> binding sites </DNA> for the <protein> GATA family </protein> of <protein> transcription factors </protein> ."
  },
  {
    "input_text": "Phosphorylation of the transcription factor NFATp inhibits its DNA binding activity in cyclosporin A-treated human B and T cells .",
    "target_text": "Phosphorylation of the <protein> transcription factor </protein> <protein> NFATp </protein> inhibits its DNA binding activity in <cell_line> cyclosporin A-treated human B </cell_line> and <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "Cyclosporin A ( CsA ) exerts its immunosuppressive effect by inhibiting the activity of nuclear factor of activated T cells ( NFAT ) , thus preventing transcriptional induction of several cytokine genes .",
    "target_text": "Cyclosporin A ( CsA ) exerts its immunosuppressive effect by inhibiting the activity of <protein> nuclear factor </protein> of activated <cell_type> T cells </cell_type> ( <protein> NFAT </protein> ) , thus preventing transcriptional induction of several cytokine genes ."
  },
  {
    "input_text": "This effect is thought to be largely mediated through inactivation of the phosphatase calcineurin , which in turn inhibits translocation of an NFAT component to the nucleus .",
    "target_text": "This effect is thought to be largely mediated through inactivation of the phosphatase <protein> calcineurin </protein> , which in turn inhibits translocation of an <protein> NFAT </protein> component to the nucleus ."
  },
  {
    "input_text": "Here we report that CsA treatment of Raji B and Jurkat T cell lines yields a phosphorylated form of NFATp that is inhibited in DNA-binding and in its ability to form an NFAT complex with Fos and Jun .",
    "target_text": "Here we report that CsA treatment of <cell_line> Raji B </cell_line> and <cell_line> Jurkat <cell_line> T cell lines </cell_line> </cell_line> yields a phosphorylated form of <protein> NFATp </protein> that is inhibited in DNA-binding and in its ability to form an <protein> NFAT complex </protein> with <protein> Fos </protein> and <protein> Jun </protein> ."
  },
  {
    "input_text": "Immunoblot analyses and metabolic labeling with [32P]orthophosphate show that CsA alters NFATp migration on SDS-polyacrylamide gel electrophoresis by increasing its phosphorylation level without affecting subcellular distribution .",
    "target_text": "Immunoblot analyses and metabolic labeling with [32P]orthophosphate show that CsA alters <protein> NFATp </protein> migration on SDS-polyacrylamide gel electrophoresis by increasing its phosphorylation level without affecting subcellular distribution ."
  },
  {
    "input_text": "Dephosphorylation by in vitro treatment with calcineurin or alkaline phosphatase restores NFATp DNA binding activity and its ability to reconstitute an NFAT complex with Fos and Jun proteins .",
    "target_text": "Dephosphorylation by in vitro treatment with <protein> calcineurin </protein> or <protein> alkaline phosphatase </protein> restores <protein> NFATp </protein> DNA binding activity and its ability to reconstitute an <protein> NFAT complex </protein> with <protein> Fos </protein> and <protein> Jun </protein> proteins ."
  },
  {
    "input_text": "These data point to a new mechanism for CsA -sensitive regulation of NFATp in which dephosphorylation is critical for DNA binding .",
    "target_text": "These data point to a new mechanism for CsA -sensitive regulation of <protein> NFATp </protein> in which dephosphorylation is critical for DNA binding ."
  },
  {
    "input_text": "Transcription factors as targets for oxidative signalling during lymphocyte activation .",
    "target_text": "<protein> Transcription factors </protein> as targets for oxidative signalling during lymphocyte activation ."
  },
  {
    "input_text": "We previously have demonstrated a requirement for oxidative events during cell cycle entry in T lymphocytes and have hypothesised that reactive oxygen species may act as intracellular signalling agents during lymphocyte activation .",
    "target_text": "We previously have demonstrated a requirement for oxidative events during cell cycle entry in <cell_type> T lymphocytes </cell_type> and have hypothesised that reactive oxygen species may act as intracellular signalling agents during lymphocyte activation ."
  },
  {
    "input_text": "In the current study , cysteamine , an aminothiol compound with antioxidant activity , has been used to further investigate the role of oxidative signalling during lymphocyte activation .",
    "target_text": "In the current study , cysteamine , an aminothiol compound with antioxidant activity , has been used to further investigate the role of oxidative signalling during lymphocyte activation ."
  },
  {
    "input_text": "Treatment of normal human peripheral blood lymphocytes with cysteamine in vitro was found to inhibit proliferation in a dose-dependent manner , with essentially complete inhibition occurring at a dose of 400 microM .",
    "target_text": "Treatment of normal <cell_type> human peripheral blood lymphocytes </cell_type> with cysteamine in vitro was found to inhibit proliferation in a dose-dependent manner , with essentially complete inhibition occurring at a dose of 400 microM ."
  },
  {
    "input_text": "This inhibitory effect was limited to the first 2 h after mitogenic activation , localizing the time-frame of action of cysteamine to within the commitment period .",
    "target_text": "This inhibitory effect was limited to the first 2 h after mitogenic activation , localizing the time-frame of action of cysteamine to within the commitment period ."
  },
  {
    "input_text": "It therefore was of interest to establish which , if any , commitment events were affected by oxidative signalling during cell cycle entry .",
    "target_text": "It therefore was of interest to establish which , if any , commitment events were affected by oxidative signalling during cell cycle entry ."
  },
  {
    "input_text": "Taking the IL-2 gene as a candidate , we examined the effect of cysteamine treatment on early gene expression during lymphocyte activation , and on the activity of transcription factors AP-1 , NF-kappa B , NF-AT and Oct1 , whose functions are required for expression of the IL-2 mRNA .",
    "target_text": "Taking the <DNA> <protein> IL-2 </protein> gene </DNA> as a candidate , we examined the effect of cysteamine treatment on <DNA> early gene </DNA> expression during lymphocyte activation , and on the activity of <protein> transcription factors </protein> <protein> AP-1 </protein> , <protein> NF-kappa B </protein> , <protein> NF-AT </protein> and <protein> Oct1 </protein> , whose functions are required for expression of the <protein> IL-2 </protein> mRNA ."
  },
  {
    "input_text": "Cysteamine treatment inhibited both expression of the IL-2 mRNA and secretion of IL-2 into the culture medium .",
    "target_text": "Cysteamine treatment inhibited both expression of the <RNA> <protein> IL-2 </protein> mRNA </RNA> and secretion of <protein> IL-2 </protein> into the culture medium ."
  },
  {
    "input_text": "The inhibitory effect of cysteamine may be mediated at least in part by an effect on transcription factor function , as the DNA binding activities of AP-1 and NF-kappa B extracted from mitogen-stimulated cells were significantly inhibited by cysteamine treatment .",
    "target_text": "The inhibitory effect of cysteamine may be mediated at least in part by an effect on <protein> transcription factor </protein> function , as the DNA binding activities of <protein> AP-1 </protein> and <protein> NF-kappa B </protein> extracted from <cell_type> mitogen-stimulated cells </cell_type> were significantly inhibited by cysteamine treatment ."
  },
  {
    "input_text": "Interestingly , Oct1 and NF-AT DNA binding activity were not affected by cysteamine treatment , suggesting that oxidative signalling processes operate in a selective manner .",
    "target_text": "Interestingly , Oct1 and NF-AT DNA binding activity were not affected by cysteamine treatment , suggesting that oxidative signalling processes operate in a selective manner ."
  },
  {
    "input_text": "The identification of regulatory proteins , such as transcription factors , as molecular targets for oxidative signalling provides further evidence to implicate oxidative signalling as being intimately involved in the G0 to G1 phase transition in T lymphocytes .",
    "target_text": "The identification of <protein> regulatory proteins </protein> , such as <protein> transcription factors </protein> , as molecular targets for oxidative signalling provides further evidence to implicate oxidative signalling as being intimately involved in the G0 to G1 phase transition in <cell_type> T lymphocytes </cell_type> ."
  },
  {
    "input_text": "Sex and age distribution of 1,25(OH)2D3 receptors in peripheral blood mononuclear cells from normal human subjects .",
    "target_text": "Sex and age distribution of <protein> 1,25(OH)2D3 receptors </protein> in <cell_type> peripheral blood mononuclear cells </cell_type> from normal human subjects ."
  },
  {
    "input_text": "Specific receptors for 1,25 Dihydroxyvitamin D3 have been described in human peripheral blood mononuclear cells ( PBMC ) .",
    "target_text": "Specific receptors for 1,25 Dihydroxyvitamin D3 have been described in human <cell_type> peripheral blood mononuclear cells </cell_type> ( <cell_type> PBMC </cell_type> ) ."
  },
  {
    "input_text": "We have tried to find out whether these receptors could show any difference in sex or age distribution .",
    "target_text": "We have tried to find out whether these receptors could show any difference in sex or age distribution ."
  },
  {
    "input_text": "Twenty two healthy men aged 21-66 yr ( mean +/- SD 41.0 +/- 13.6 ) and nineteen healthy women aged 22-60 yr ( 38.9 +/- 13.9 ) have been studied .",
    "target_text": "Twenty two healthy men aged 21-66 yr ( mean +/- SD 41.0 +/- 13.6 ) and nineteen healthy women aged 22-60 yr ( 38.9 +/- 13.9 ) have been studied ."
  },
  {
    "input_text": "The mean dissociation constant ( Kd ) was similar in both sexes ( 1.35 +/- 0.70 x 10(-10) M in males , 1.13 +/- 0.66 x 10(-10) M in females ) , but the concentration of binding sites ( Nmax ) was significantly lower in females ( 2.32 +/- 0.92 fmol/10 ( 7 ) PBMC vs 4.43 +/- 1.38 fmol/10(7) PBMC in males ; p = 0.0001 ) .",
    "target_text": "The mean dissociation constant ( Kd ) was similar in both sexes ( 1.35 +/- 0.70 x 10(-10) M in males , 1.13 +/- 0.66 x 10(-10) M in females ) , but the concentration of binding sites ( Nmax ) was significantly lower in females ( 2.32 +/- 0.92 fmol/10 ( 7 ) <cell_type> PBMC </cell_type> vs 4.43 +/- 1.38 fmol/10(7) <cell_type> PBMC </cell_type> in males ; p = 0.0001 ) ."
  },
  {
    "input_text": "Neither Kd nor Nmax were significantly correlated with age .",
    "target_text": "Neither Kd nor Nmax were significantly correlated with age ."
  },
  {
    "input_text": "No difference was found between pre and post menopausal women .",
    "target_text": "No difference was found between pre and post menopausal women ."
  },
  {
    "input_text": "Further studies are needed to elucidate if this sex difference in PBMC receptors for 1.25 Dihydroxyvitamin D3 is of any pathophysiological relevance .",
    "target_text": "Further studies are needed to elucidate if this sex difference in <protein> <cell_type> PBMC </cell_type> receptors </protein> for 1.25 Dihydroxyvitamin D3 is of any pathophysiological relevance ."
  },
  {
    "input_text": "Expression of Id2 and Id3 mRNA in human lymphocytes .",
    "target_text": "Expression of Id2 and Id3 mRNA in <cell_type> human lymphocytes </cell_type> ."
  },
  {
    "input_text": "Helix-loop-helix ( HLH ) transcription factors are involved in cellular growth and differentiation .",
    "target_text": "<protein> <protein> Helix-loop-helix </protein> ( <protein> HLH </protein> ) transcription factors </protein> are involved in cellular growth and differentiation ."
  },
  {
    "input_text": "The Id ( inhibitor of DNA binding and differentiation ) HLH proteins , in a dominantly negative fashion , regulate transcriptional activities of basic HLH proteins .",
    "target_text": "The <protein> Id </protein> ( inhibitor of DNA binding and differentiation ) <protein> HLH proteins </protein> , in a dominantly negative fashion , regulate transcriptional activities of <protein> basic HLH proteins </protein> ."
  },
  {
    "input_text": "We examined by northern hybridization the expression of Id2 and Id3 mRNA in human leukemia/lymphoma lines and patient samples , as well as resting and activated normal human lymphocytes from peripheral blood ( PBL ) .",
    "target_text": "We examined by northern hybridization the expression of Id2 and Id3 mRNA in <cell_line> human leukemia/lymphoma lines </cell_line> and patient samples , as well as resting and <cell_line> activated normal human lymphocytes </cell_line> from peripheral blood ( <cell_type> PBL </cell_type> ) ."
  },
  {
    "input_text": "The Id2 mRNA was abundantly expressed in 5/12 T-cell and 3/4 B-cell lines , and Id3 mRNA was detected in 4/12 T-cell and 3/4 B-cell lines .",
    "target_text": "The <RNA> <protein> Id2 </protein> mRNA </RNA> was abundantly expressed in <cell_line> 5/12 T-cell </cell_line> and <cell_line> 3/4 B-cell lines </cell_line> , and <RNA> <protein> Id3 </protein> mRNA </RNA> was detected in <cell_line> 4/12 T-cell </cell_line> and <cell_line> 3/4 B-cell lines </cell_line> ."
  },
  {
    "input_text": "Interestingly , Id2 , but not Id3 , mRNA was strongly expressed in 4/5 T-cell lines infected with human T-cell leukemia virus type I ( HTLV-I ) ( ATL-1k , MT-2 , S-LB1 ) and type II ( Mo ) .",
    "target_text": "Interestingly , <protein> <RNA> Id2 </RNA> </protein> , but not <protein> <RNA> Id3 </RNA> </protein> , mRNA was strongly expressed in <cell_line> 4/5 T-cell lines </cell_line> infected with human T-cell leukemia virus type I ( HTLV-I ) ( <cell_line> ATL-1k </cell_line> , <cell_line> MT-2 </cell_line> , <cell_line> S-LB1 </cell_line> ) and type II ( <cell_line> Mo </cell_line> ) ."
  },
  {
    "input_text": "Another unexpected finding was that T-cell leukemias and T-cell lines often expressed either Id2 or Id3 mRNA .",
    "target_text": "Another unexpected finding was that T-cell leukemias and <cell_line> T-cell lines </cell_line> often expressed either <protein> <RNA> Id2 </RNA> </protein> or <RNA> <protein> Id3 </protein> mRNA </RNA> ."
  },
  {
    "input_text": "In addition , resting PBL constitutively expressed prominent levels of Id2 mRNA , but not Id3 mRNA .",
    "target_text": "In addition , <cell_type> resting <cell_type> PBL </cell_type> </cell_type> constitutively expressed prominent levels of <RNA> <protein> Id2 </protein> mRNA </RNA> , but not <RNA> <protein> Id3 </protein> mRNA </RNA> ."
  },
  {
    "input_text": "Upon PHA -stimulation , Id2 expression decreased and Id3 levels increased with biphasic kinetics .",
    "target_text": "Upon <protein> PHA </protein> -stimulation , <protein> Id2 </protein> expression decreased and <protein> Id3 </protein> levels increased with biphasic kinetics ."
  },
  {
    "input_text": "Taken together , our studies revealed three unexpected findings which require further analysis : ( 1 ) expression of Id2 mRNA is often associated with lymphocytic transformation by HTLV-I or -II ; ( 2 ) T-cells usually express either Id2 or Id3 mRNA , but B-cells often express both simultaneously ; ( 3 ) non-dividing , normal PBL express high levels of Id2 and no Id3 mRNA ; and with the onset of cellular proliferation , levels of Id2 mRNA decrease while levels of Id3 mRNA increase , suggesting that regulation of expression of these closely related genes is disparate .",
    "target_text": "Taken together , our studies revealed three unexpected findings which require further analysis : ( 1 ) expression of <RNA> <protein> Id2 </protein> mRNA </RNA> is often associated with lymphocytic transformation by HTLV-I or -II ; ( 2 ) T-cells usually express either <protein> Id2 </protein> or <RNA> <protein> Id3 </protein> mRNA </RNA> , but B-cells often express both simultaneously ; ( 3 ) non-dividing , normal <cell_type> PBL </cell_type> express high levels of <protein> Id2 </protein> and no <RNA> <protein> Id3 </protein> mRNA </RNA> ; and with the onset of cellular proliferation , levels of <RNA> <protein> Id2 </protein> mRNA </RNA> decrease while levels of <RNA> <protein> Id3 </protein> mRNA </RNA> increase , suggesting that regulation of expression of these closely related <DNA> genes </DNA> is disparate ."
  },
  {
    "input_text": "Salicylates inhibit lipopolysaccharide -induced transcriptional activation of the tissue factor gene in human monocytic cells .",
    "target_text": "Salicylates inhibit lipopolysaccharide -induced transcriptional activation of the tissue factor gene in <cell_type> human monocytic cells </cell_type> ."
  },
  {
    "input_text": "Binding of plasma Factor VII/VIIa to the tissue factor ( TF ) receptor initiates the coagulation protease cascades .",
    "target_text": "Binding of <protein> plasma Factor VII/VIIa </protein> to the <protein> tissue factor ( TF ) receptor </protein> initiates the <protein> coagulation protease </protein> cascades ."
  },
  {
    "input_text": "TF expression by circulating monocytes is associated with thrombotic and inflammatory complications in a variety of diseases .",
    "target_text": "TF expression by <cell_type> circulating monocytes </cell_type> is associated with thrombotic and inflammatory complications in a variety of diseases ."
  },
  {
    "input_text": "Transcriptional activation of the human TF gene in monocytic cells exposed to bacterial lipopolysaccharide ( LPS ) is mediated by binding of c-Rel /p65 heterodimers to a kappa B site in the TF promoter .",
    "target_text": "Transcriptional activation of the <DNA> human TF gene </DNA> in <cell_type> monocytic cells </cell_type> exposed to bacterial lipopolysaccharide ( LPS ) is mediated by binding of <protein> c-Rel /p65 heterodimers </protein> to a <DNA> kappa B site </DNA> in the <DNA> TF promoter </DNA> ."
  },
  {
    "input_text": "Here , we report that a family of anti-inflammatory agents , known as the salicylates , inhibited LPS induction of TF activity and TF gene transcription in human monocytes and monocytic THP-1 cells at clinically relevant doses .",
    "target_text": "Here , we report that a family of anti-inflammatory agents , known as the salicylates , inhibited LPS induction of TF activity and <DNA> TF gene </DNA> transcription in <cell_type> human monocytes </cell_type> and <cell_line> monocytic THP-1 cells </cell_line> at clinically relevant doses ."
  },
  {
    "input_text": "Furthermore , sodium salicylate blocked the LPS -induced proteolytic degradation of I kappa B alpha , which prevented the nuclear translocation of c-Rel /p65 heterodimers .",
    "target_text": "Furthermore , sodium salicylate blocked the LPS -induced proteolytic degradation of <protein> I kappa B alpha </protein> , which prevented the nuclear translocation of <protein> c-Rel /p65 heterodimers </protein> ."
  },
  {
    "input_text": "In contrast , two other nonsteroidal anti-inflammatory drugs , ibuprofen and indomethacin , did not inhibit LPS induction of the TF gene .",
    "target_text": "In contrast , two other nonsteroidal anti-inflammatory drugs , ibuprofen and indomethacin , did not inhibit LPS induction of the <DNA> TF gene </DNA> ."
  },
  {
    "input_text": "These results indicated that salicylates inhibited LPS induction of TF gene transcription in monocytic cells by preventing nuclear translocation of c-Rel /p65 heterodimers .",
    "target_text": "These results indicated that salicylates inhibited LPS induction of <DNA> TF gene </DNA> transcription in <cell_type> monocytic cells </cell_type> by preventing nuclear translocation of <protein> c-Rel /p65 heterodimers </protein> ."
  },
  {
    "input_text": "The clinical benefits of salicylates in the treatment of several diseases , including atherosclerosis and rheumatoid arthritis , may be related to their ability to reduce monocyte gene expression .",
    "target_text": "The clinical benefits of salicylates in the treatment of several diseases , including atherosclerosis and rheumatoid arthritis , may be related to their ability to reduce monocyte gene expression ."
  },
  {
    "input_text": "Activation of the signal transducer and transcription ( STAT ) signaling pathway in a primary T cell response .",
    "target_text": "Activation of the signal transducer and transcription ( <protein> STAT </protein> ) signaling pathway in a primary T cell response ."
  },
  {
    "input_text": "Critical role for IL-6 .",
    "target_text": "Critical role for <protein> IL-6 </protein> ."
  },
  {
    "input_text": "The T cell activation is initiated by interaction of specific Ags with TCR , followed by activation of intracellular biochemical events leading to activation of several genes .",
    "target_text": "The T cell activation is initiated by interaction of specific <protein> Ags </protein> with <protein> TCR </protein> , followed by activation of intracellular biochemical events leading to activation of several genes ."
  },
  {
    "input_text": "The activation of signal transducer and activator of transcription ( STAT ) proteins in a primary TCR -mediated activation of T cells have been explored .",
    "target_text": "The activation of signal transducer and activator of <protein> transcription ( STAT ) proteins </protein> in a primary <protein> TCR </protein> -mediated activation of <cell_type> T cells </cell_type> have been explored ."
  },
  {
    "input_text": "In purified human peripheral blood T cells , nuclear STAT proteins were activated approximately 3 h after activation by cross-linked anti-CD3 Abs .",
    "target_text": "In <cell_type> purified human peripheral blood <cell_type> T cells </cell_type> </cell_type> , <protein> nuclear STAT proteins </protein> were activated approximately 3 h after activation by cross-linked <protein> anti-CD3 Abs </protein> ."
  },
  {
    "input_text": "These STAT proteins were detected by using the IFN-gamma-activated sequence ( GAS ) and related oligonucleotides as probes in electrophoretic mobility shift assay .",
    "target_text": "These <protein> STAT proteins </protein> were detected by using the <DNA> IFN-gamma-activated sequence </DNA> ( <DNA> GAS </DNA> ) and related oligonucleotides as probes in electrophoretic mobility shift assay ."
  },
  {
    "input_text": "Analysis of the nuclear extracts with anti-STAT Abs indicated that they contained STAT-3 and additional proteins crossreactive with the STAT family .",
    "target_text": "Analysis of the nuclear extracts with <protein> anti-STAT Abs </protein> indicated that they contained <protein> STAT-3 </protein> and additional proteins crossreactive with the <protein> STAT family </protein> ."
  },
  {
    "input_text": "The induction of STAT activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A , thus indicating that the induction was due to a secondary factor produced by the activated T cells .",
    "target_text": "The induction of <protein> STAT </protein> activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A , thus indicating that the induction was due to a <protein> secondary factor </protein> produced by the activated <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "As neutralizing anti- IL-6 Abs effectively down-regulated the early induction of STAT proteins and as exogenously added IL-6 rapidly activated DNA binding similar to TCR -mediated bindings , it can be concluded that IL-6 is the factor responsible for the activation of STAT proteins in a primary T cell response .",
    "target_text": "As <protein> neutralizing anti- <protein> IL-6 </protein> Abs </protein> effectively down-regulated the early induction of <protein> STAT proteins </protein> and as exogenously added <protein> IL-6 </protein> rapidly activated DNA binding similar to <protein> TCR </protein> -mediated bindings , it can be concluded that <protein> IL-6 </protein> is the factor responsible for the activation of <protein> STAT proteins </protein> in a primary T cell response ."
  },
  {
    "input_text": "The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus .",
    "target_text": "The normal cell cycle activation program is exploited during the infection of <cell_type> quiescent B lymphocytes </cell_type> by Epstein-Barr virus ."
  },
  {
    "input_text": "B lymphocytes in the peripheral circulation are maintained in a non-proliferative state .",
    "target_text": "<cell_type> B lymphocytes </cell_type> in the peripheral circulation are maintained in a non-proliferative state ."
  },
  {
    "input_text": "Antigen recognition stimulates limited proliferation , whereas infection with Epstein-Barr virus ( EBV ) results in continual proliferation and the outgrowth of immortal cell lines .",
    "target_text": "Antigen recognition stimulates limited proliferation , whereas infection with Epstein-Barr virus ( EBV ) results in continual proliferation and the outgrowth of <cell_line> immortal cell lines </cell_line> ."
  },
  {
    "input_text": "Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested , we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells .",
    "target_text": "Because it is not clear at which point in cell cycle the <cell_type> peripheral <cell_type> B lymphocytes </cell_type> </cell_type> are arrested , we characterized the expression of several <DNA> cell cycle-associated genes </DNA> in quiescent and stimulated cells ."
  },
  {
    "input_text": "We show that the expression of four cell genes , cdc-2 , cyclin E , CD23 , and cyclin D2 , are up-regulated approximately 100-fold as a result of EBV -mediated immortalization .",
    "target_text": "We show that the expression of four <DNA> cell genes </DNA> , <DNA> cdc-2 </DNA> , <DNA> cyclin E </DNA> , <DNA> CD23 </DNA> , and <DNA> cyclin D2 </DNA> , are up-regulated approximately 100-fold as a result of EBV -mediated immortalization ."
  },
  {
    "input_text": "Because these genes play a positive role in cell proliferation , we suggest that this regulatory switch contributes to controlling entry into the cell cycle .",
    "target_text": "Because these genes play a positive role in cell proliferation , we suggest that this regulatory switch contributes to controlling entry into the cell cycle ."
  },
  {
    "input_text": "Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40 , anti-IgM , and IL4 , or EBV results in the rapid expression of the same four genes , suggesting that , after infection , EBV exploits the normal program of B-lymphocyte cell cycle activation .",
    "target_text": "Transient stimulation of <cell_type> quiescent <cell_type> B lymphocytes </cell_type> </cell_type> with either a cocktail of <protein> anti-CD40 </protein> , <protein> anti-IgM </protein> , and <protein> IL4 </protein> , or EBV results in the rapid expression of the same four genes , suggesting that , after infection , EBV exploits the normal program of <cell_type> B-lymphocyte </cell_type> cell cycle activation ."
  },
  {
    "input_text": "Expression of the chemokine receptor BLR2/EBI1 is specifically transactivated by Epstein-Barr virus nuclear antigen 2 .",
    "target_text": "Expression of the <protein> chemokine receptor </protein> <protein> BLR2/EBI1 </protein> is specifically transactivated by <protein> Epstein-Barr virus nuclear antigen 2 </protein> ."
  },
  {
    "input_text": "In our attempt to identify chemokine receptors that are related to Burkitt 's lymphoma receptor 1 ( BLR1 ) and are expressed in activated lymphocytes we used RT-PCR resulting in the isolation of a cDNA encoding a seven transmembrane receptor termed BLR2 .",
    "target_text": "In our attempt to identify <protein> chemokine receptors </protein> that are related to <protein> Burkitt 's lymphoma receptor 1 </protein> ( <protein> BLR1 </protein> ) and are expressed in <cell_type> activated lymphocytes </cell_type> we used RT-PCR resulting in the isolation of a cDNA encoding a <protein> seven transmembrane receptor </protein> termed <protein> BLR2 </protein> ."
  },
  {
    "input_text": "The protein shows significant sequence similarities to the family of G-protein coupled chemokine receptors and turned out to be identical to the recently described receptor EBI1 .",
    "target_text": "The protein shows significant sequence similarities to the family of <protein> <protein> G-protein </protein> coupled <protein> chemokine receptors </protein> </protein> and turned out to be identical to the recently described <protein> receptor EBI1 </protein> ."
  },
  {
    "input_text": "Northern blot analysis revealed that BLR2 mRNA could be highly stimulated in mitogen- and anti-CD3- treated peripheral blood lymphocytes .",
    "target_text": "Northern blot analysis revealed that <RNA> <protein> BLR2 </protein> mRNA </RNA> could be highly stimulated in mitogen- and anti-CD3- treated peripheral blood lymphocytes ."
  },
  {
    "input_text": "BLR2 -specific mRNA could be detected in all Epstein-Barr virus positive B cell lines .",
    "target_text": "<RNA> <protein> BLR2 </protein> -specific mRNA </RNA> could be detected in all <cell_line> Epstein-Barr virus positive B cell lines </cell_line> ."
  },
  {
    "input_text": "We show that transcription of the BLR2 gene could be specifically induced in Epstein-Barr virus negative BL 41 cells via estrogen-mediated activation of Epstein-Barr virus nuclear antigen 2 , a key regulator of viral and cellular genes in immortalized B cells .",
    "target_text": "We show that transcription of the <DNA> <protein> BLR2 </protein> gene </DNA> could be specifically induced in <cell_line> Epstein-Barr virus negative BL 41 cells </cell_line> via estrogen-mediated activation of <protein> Epstein-Barr virus nuclear antigen 2 </protein> , a key regulator of <DNA> <DNA> viral </DNA> and <DNA> cellular genes </DNA> </DNA> in <cell_line> immortalized B cells </cell_line> ."
  },
  {
    "input_text": "Our data suggest an involvement of BLR2 in the regulation of migration in activated lymphocytes and in viral pathogenesis .",
    "target_text": "Our data suggest an involvement of <protein> BLR2 </protein> in the regulation of migration in <cell_type> activated lymphocytes </cell_type> and in viral pathogenesis ."
  },
  {
    "input_text": "A central role for a single c-Myb binding site in a thymic locus control region .",
    "target_text": "A central role for a <DNA> single c-Myb binding site </DNA> in a <DNA> thymic locus control region </DNA> ."
  },
  {
    "input_text": "Locus control regions ( LCRs ) are powerful assemblies of cis elements that organize the actions of cell-type-specific trans-acting factors .",
    "target_text": "<DNA> Locus control regions </DNA> ( <DNA> LCRs </DNA> ) are powerful assemblies of <DNA> cis elements </DNA> that organize the actions of <protein> cell-type-specific trans-acting factors </protein> ."
  },
  {
    "input_text": "A 2.3-kb LCR in the human adenosine deaminase ( ADA ) gene first intron , which controls expression in thymocytes , is composed of a 200-bp enhancer domain and extended flanking sequences that facilitate activation from within chromatin .",
    "target_text": "A <protein> 2.3-kb LCR </protein> in the <DNA> <DNA> human adenosine deaminase ( ADA ) gene </DNA> first intron </DNA> , which controls expression in <cell_type> thymocytes </cell_type> , is composed of a <DNA> 200-bp enhancer domain </DNA> and extended flanking sequences that facilitate activation from within <DNA> chromatin </DNA> ."
  },
  {
    "input_text": "Prior analyses have demonstrated that the enhancer contains a 28-bp core region and local adjacent augmentative cis elements .",
    "target_text": "Prior analyses have demonstrated that the <DNA> enhancer </DNA> contains a <DNA> 28-bp core region </DNA> and local adjacent augmentative <DNA> cis elements </DNA> ."
  },
  {
    "input_text": "We now show that the core contains a single critical c-Myb binding site .",
    "target_text": "We now show that the core contains a single critical <DNA> c-Myb binding site </DNA> ."
  },
  {
    "input_text": "In both transiently cotransfected human cells and stable chromatin-integrated yeast cells , c-Myb strongly transactivated reporter constructs that contained polymerized core sequences .",
    "target_text": "In both <cell_line> transiently cotransfected human cells </cell_line> and stable <cell_line> chromatin-integrated yeast cells </cell_line> , <protein> c-Myb </protein> strongly <DNA> transactivated reporter constructs </DNA> that contained <DNA> polymerized core sequences </DNA> ."
  },
  {
    "input_text": "c-Myb protein was strongly evident in T lymphoblasts in which the enhancer was active and was localized within discrete nuclear structures .",
    "target_text": "<protein> <protein> c-Myb </protein> protein </protein> was strongly evident in <cell_type> T lymphoblasts </cell_type> in which the <DNA> enhancer </DNA> was active and was localized within discrete nuclear structures ."
  },
  {
    "input_text": "Fetal murine thymus exhibited a striking concordance of endogenous c-myb expression with that of mouse ADA and human ADA LCR -directed transgene expression .",
    "target_text": "Fetal murine thymus exhibited a striking concordance of endogenous <DNA> c-myb </DNA> expression with that of <DNA> mouse ADA </DNA> and <DNA> human ADA LCR </DNA> -directed transgene expression ."
  },
  {
    "input_text": "Point mutation of the c-Myb site within the intact 2.3-kb LCR severely attenuated enhancer activity in transfections and LCR activity in transgenic thymocytes .",
    "target_text": "Point mutation of the <DNA> <protein> c-Myb </protein> site </DNA> within the intact <protein> 2.3-kb LCR </protein> severely attenuated enhancer activity in transfections and <DNA> LCR </DNA> activity in <cell_line> transgenic <cell_type> thymocytes </cell_type> </cell_line> ."
  },
  {
    "input_text": "Within the context of a complex enhancer and LCR , c-Myb can act as an organizer of thymocyte-specific gene expression via a single binding site .",
    "target_text": "Within the context of a <DNA> complex enhancer </DNA> and <DNA> LCR </DNA> , <protein> c-Myb </protein> can act as an organizer of <DNA> thymocyte-specific gene </DNA> expression via a single binding site ."
  },
  {
    "input_text": "A regulatory element in the human interleukin 2 gene promoter is a binding site for the zinc finger proteins Sp1 and EGR-1 .",
    "target_text": "A <DNA> regulatory element </DNA> in the <DNA> human interleukin 2 gene promoter </DNA> is a <DNA> binding site </DNA> for the <protein> zinc finger proteins </protein> <protein> Sp1 </protein> and <protein> EGR-1 </protein> ."
  },
  {
    "input_text": "Activation of the interleukin 2 ( IL-2 ) gene after antigen recognition is a critical event for T cell proliferation and effector function .",
    "target_text": "Activation of the <DNA> <protein> interleukin 2 </protein> ( <protein> IL-2 </protein> ) gene </DNA> after antigen recognition is a critical event for T cell proliferation and effector function ."
  },
  {
    "input_text": "Prior studies have identified several transcription factors that contribute to the activity of the IL-2 promoter in stimulated T lymphocytes .",
    "target_text": "Prior studies have identified several <protein> transcription factors </protein> that contribute to the activity of the <DNA> <protein> IL-2 </protein> promoter </DNA> in <cell_type> stimulated T lymphocytes </cell_type> ."
  },
  {
    "input_text": "Here we describe a novel regulatory element within the IL-2 promoter located immediately upstream of the nuclear factor of activated T cell ( NFAT ) domain .",
    "target_text": "Here we describe a novel <DNA> regulatory element </DNA> within the <DNA> IL-2 promoter </DNA> located immediately upstream of the <DNA> <protein> nuclear factor of activated T cell </protein> ( <protein> NFAT </protein> ) domain </DNA> ."
  },
  {
    "input_text": "This region ( termed the zinc finger protein binding region ( ZIP ) ) serves as binding site for two differently regulated zinc finger proteins : the constitutively expressed transcription factor Sp1 and the inducible early growth response protein EGR-1 .",
    "target_text": "This region ( termed the <DNA> zinc finger protein binding region </DNA> ( <DNA> ZIP </DNA> ) ) serves as binding site for two differently regulated <protein> zinc finger proteins </protein> : the <protein> constitutively expressed transcription factor </protein> <protein> Sp1 </protein> and the <protein> inducible early growth response protein </protein> <protein> EGR-1 </protein> ."
  },
  {
    "input_text": "In unstimulated cells which do not secrete IL-2 , only Sp1 binds to this region , while in stimulated IL-2 secreting cells the inducible EGR-1 protein recognizes this element .",
    "target_text": "In <cell_type> unstimulated cells </cell_type> which do not secrete <protein> IL-2 </protein> , only <protein> Sp1 </protein> binds to this region , while in <cell_line> stimulated <protein> IL-2 </protein> secreting cells </cell_line> the <protein> inducible <protein> EGR-1 </protein> protein </protein> recognizes this element ."
  },
  {
    "input_text": "In Jurkat T cells , the ZIP site serves as an activator for IL-2 gene expression , and a combination of ZIP and NFAT binding sites is required for maximal IL-2 promoter activity .",
    "target_text": "In <cell_line> Jurkat T cells </cell_line> , the <DNA> <DNA> ZIP </DNA> site </DNA> serves as an activator for <protein> IL-2 </protein> gene expression , and a combination of <DNA> ZIP </DNA> and <DNA> <protein> NFAT </protein> binding sites </DNA> is required for maximal <DNA> <protein> IL-2 </protein> promoter </DNA> activity ."
  },
  {
    "input_text": "These results suggest a critical role of the ZIP site for IL-2 promoter activity .",
    "target_text": "These results suggest a critical role of the <DNA> ZIP site </DNA> for <DNA> <protein> IL-2 </protein> promoter </DNA> activity ."
  },
  {
    "input_text": "Activation of the HIV-1 enhancer by the LEF-1 HMG protein on nucleosome-assembled DNA in vitro .",
    "target_text": "Activation of the <DNA> HIV-1 enhancer </DNA> by the <protein> LEF-1 HMG protein </protein> on <DNA> nucleosome-assembled DNA </DNA> in vitro ."
  },
  {
    "input_text": "Lymphoid enhancer-binding factor 1 ( LEF-1 ) is a regulatory high mobility group ( HMG ) protein that activates the T cell receptor alpha ( TCR alpha ) enhancer in a context-restricted manner in T cells .",
    "target_text": "<protein> Lymphoid enhancer-binding factor 1 </protein> ( <protein> LEF-1 </protein> ) is a <protein> regulatory high mobility group ( HMG ) protein </protein> that activates the <DNA> <protein> T cell receptor alpha </protein> ( <protein> TCR alpha </protein> ) enhancer </DNA> in a context-restricted manner in <cell_type> T cells </cell_type> ."
  },
  {
    "input_text": "In this paper we demonstrate that the distal region of the human immunodeficiency virus-1 ( HIV-1 ) enhancer , which contains DNA-binding sites for LEF-1 and Ets-1 , also provides a functional context for activation by LEF-1 .",
    "target_text": "In this paper we demonstrate that the distal region of the <DNA> human immunodeficiency virus-1 ( HIV-1 ) enhancer </DNA> , which contains <DNA> DNA-binding sites </DNA> for <protein> LEF-1 </protein> and Ets-1 , also provides a functional context for activation by <protein> LEF-1 </protein> ."
  },
  {
    "input_text": "First , we show that mutations in the LEF-1 -binding site inhibit the activity of multimerized copies of the HIV-1 enhancer in Jurkat T cells , and that LEF-1 /GAL4 can activate a GAL4-substituted HIV-1 enhancer 80- to 100-fold in vivo .",
    "target_text": "First , we show that mutations in the <DNA> <protein> LEF-1 </protein> -binding site </DNA> inhibit the activity of <DNA> multimerized copies </DNA> of the <DNA> HIV-1 enhancer </DNA> in <cell_line> Jurkat T cells </cell_line> , and that <protein> <protein> LEF-1 </protein> /GAL4 </protein> can activate a <DNA> GAL4-substituted <DNA> HIV-1 enhancer </DNA> </DNA> 80- to 100-fold in vivo ."
  },
  {
    "input_text": "Second , recombinant LEF-1 is shown to activate HIV-1 transcription on chromatin-assembled DNA in vitro .",
    "target_text": "Second , <protein> recombinant <protein> LEF-1 </protein> </protein> is shown to activate HIV-1 transcription on <DNA> chromatin-assembled DNA </DNA> in vitro ."
  },
  {
    "input_text": "By using a nucleosome -assembly system derived from Drosophila embryos , we find that the packaging of DNA into chromatin in vitro strongly represses HIV-1 transcription and that repression can be counteracted efficiently by preincubation of the DNA with LEF-1 ( or LEF-1 and Ets-1 ) supplemented with fractions containing the promoter-binding protein , Sp1 .",
    "target_text": "By using a <protein> nucleosome </protein> -assembly system derived from Drosophila embryos , we find that the packaging of DNA into <DNA> chromatin </DNA> in vitro strongly represses HIV-1 transcription and that repression can be counteracted efficiently by preincubation of the DNA with <protein> LEF-1 </protein> ( or <protein> LEF-1 </protein> and <protein> Ets-1 </protein> ) supplemented with fractions containing the <protein> promoter-binding protein </protein> , <protein> Sp1 </protein> ."
  },
  {
    "input_text": "Addition of TFE-3 , which binds to an E-box motif upstream of the LEF-1 and Ets-1 sites , further augments transcription in this system .",
    "target_text": "Addition of <protein> TFE-3 </protein> , which binds to an <DNA> E-box motif </DNA> upstream of the LEF-1 and Ets-1 sites , further augments transcription in this system ."
  },
  {
    "input_text": "Individually or collectively , none of the three enhancer-binding proteins ( LEF-1 , Ets-1 , and TFE-3 ) could activate transcription in the absence of Sp1 .",
    "target_text": "Individually or collectively , none of the three <protein> enhancer-binding proteins </protein> ( <protein> LEF-1 </protein> , <protein> Ets-1 </protein> , and <protein> TFE-3 </protein> ) could activate transcription in the absence of <protein> Sp1 </protein> ."
  },
  {
    "input_text": "A truncation mutant of LEF-1 ( HMG-88 ) , which contains the HMG box but lacks the trans-activation domain , did not activate transcription from nucleosomal DNA , indicating that bending of DNA by the HMG domain is not sufficient to activate transcription in vitro .",
    "target_text": "A <protein> truncation mutant </protein> of <protein> LEF-1 </protein> ( <protein> HMG-88 </protein> ) , which contains the <protein> HMG box </protein> but lacks the <protein> trans-activation domain </protein> , did not activate transcription from <DNA> nucleosomal DNA </DNA> , indicating that bending of DNA by the <protein> HMG domain </protein> is not sufficient to activate transcription in vitro ."
  },
  {
    "input_text": "We conclude that transcription activation by LEF-1 in vitro is a chromatin -dependent process that requires a functional trans-activation domain in addition to the HMG domain .",
    "target_text": "We conclude that transcription activation by <protein> LEF-1 </protein> in vitro is a <DNA> chromatin </DNA> -dependent process that requires a functional <protein> trans-activation domain </protein> in addition to the <protein> HMG domain </protein> ."
  },
  {
    "input_text": "HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells [ published erratum appears in J Biol Chem 1995 Dec 1 ; 270 ( 48 ) : 29038 ]",
    "target_text": "<protein> HIV-1 envelope glycoproteins </protein> induce activation of activated <protein> protein-1 </protein> in <cell_type> CD4+ <cell_type> T cells </cell_type> </cell_type> [ published erratum appears in J Biol Chem 1995 Dec 1 ; 270 ( 48 ) : 29038 ]"
  },
  {
    "input_text": "Activation of CD4 positive T cells is a primary requirement for human immunodeficiency virus ( HIV ) entry , efficient HIV replication , and progression to AIDS , Utilizing CD4 positive T cell lines and purified T cells from normal individuals , we have demonstrated that native envelope glycoproteins of HIV , gp 160 , can induce activation of transcription factor , activated protein-1 ( AP-1 ) .",
    "target_text": "Activation of <cell_type> CD4 positive <cell_type> T cells </cell_type> </cell_type> is a primary requirement for human immunodeficiency virus ( HIV ) entry , efficient HIV replication , and progression to AIDS , Utilizing <cell_line> CD4 positive T cell lines </cell_line> and <cell_type> purified <cell_type> T cells </cell_type> </cell_type> from normal individuals , we have demonstrated that <protein> native envelope glycoproteins </protein> of HIV , <protein> gp 160 </protein> , can induce activation of <protein> transcription factor , activated protein-1 </protein> ( <protein> AP-1 </protein> ) ."
  },
  {
    "input_text": "The stimulatory effects of gp160 are mediated through the CD4 molecule , since treatment of gp160 with soluble CD4-IgG abrogates its activity , and CD4 negative T cell lines fail to be stimulated with gp160 .",
    "target_text": "The stimulatory effects of <protein> gp160 </protein> are mediated through the <protein> CD4 molecule </protein> , since treatment of <protein> gp160 </protein> with soluble <protein> CD4-IgG </protein> abrogates its activity , and <cell_line> CD4 negative T cell lines </cell_line> fail to be stimulated with <protein> gp160 </protein> ."
  },
  {
    "input_text": "Immunoprecipitation of the gp 160 -induced nuclear extracts with polyclonal antibodies to Fos and Jun proteins indicates that AP-1 complex is comprised of members of these family of proteins .",
    "target_text": "Immunoprecipitation of the <protein> gp 160 </protein> -induced nuclear extracts with <protein> polyclonal antibodies </protein> to <protein> Fos </protein> and <protein> Jun proteins </protein> indicates that <protein> <protein> AP-1 </protein> complex </protein> is comprised of members of these family of proteins ."
  },
  {
    "input_text": "The gp160 -induced AP-1 complex is dependent upon protein tyrosine phosphorylation and is protein synthesis-independent .",
    "target_text": "The <protein> <protein> gp160 </protein> -induced <protein> AP-1 </protein> complex </protein> is dependent upon protein tyrosine phosphorylation and is protein synthesis-independent ."
  },
  {
    "input_text": "This stimulation can also be abolished by inhibitors of protein kinase C , but it is unaffected by calcium channel blocker or cyclosporine A .",
    "target_text": "This stimulation can also be abolished by inhibitors of <protein> protein kinase C </protein> , but it is unaffected by calcium channel blocker or cyclosporine A ."
  },
  {
    "input_text": "This gp160 treatment adversely affects the functional capabilities of T cells : pre-treatment of CD4+ T cells with gp160 for 4 h at 37 degrees C inhibited anti-CD3 -induced interleukin-2 secretion .",
    "target_text": "This <protein> gp160 </protein> treatment adversely affects the functional capabilities of <cell_type> T cells </cell_type> : pre-treatment of <cell_type> CD4+ <cell_type> T cells </cell_type> </cell_type> with <protein> gp160 </protein> for 4 h at 37 degrees C inhibited <protein> anti-CD3 </protein> -induced <protein> interleukin-2 </protein> secretion ."
  },
  {
    "input_text": "Effects similar to gp160 were seen with anti-CD4 mAb .",
    "target_text": "Effects similar to <protein> gp160 </protein> were seen with <protein> anti-CD4 mAb </protein> ."
  },
  {
    "input_text": "The aberrant activation of AP-1 by gp160 in CD4 positive T cells could result in up-regulation of cytokines containing AP-1 sites , e.g. interleukin-3 and granulocyte macrophage colony-stimulating factor , and concurrently lead to T cell unresponsiveness by inhibiting interleukin-2 secretion .",
    "target_text": "The aberrant activation of <protein> AP-1 </protein> by <protein> gp160 </protein> in <cell_type> CD4 positive <cell_type> T cells </cell_type> </cell_type> could result in up-regulation of <protein> cytokines </protein> containing <DNA> <protein> AP-1 </protein> sites </DNA> , e.g. <protein> interleukin-3 </protein> and <protein> granulocyte macrophage colony-stimulating factor </protein> , and concurrently lead to <cell_type> T cell </cell_type> unresponsiveness by inhibiting <protein> interleukin-2 </protein> secretion ."
  }
]